141 results on '"Chih-Ping Han"'
Search Results
2. The status of KRAS mutations in primary ovarian clear cell carcinoma: An analysis of 17 Taiwanese patients
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Pi-Chieh Wang, Wan-Ru Chao, Wen-Chih Tsai, Yu-Hsuan Lin, Gwo-Tarng Sheu, and Chih-Ping Han
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Gynecology and obstetrics ,RG1-991 - Published
- 2023
- Full Text
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3. High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
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Wan-Ru Chao, Yi-Ju Lee, Ming-Yung Lee, Gwo-Tarng Sheu, and Chih-Ping Han
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Mucinous ovarian carcinoma ,BRAF gene ,Mutation ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. Materials and methods: 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results: Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Conclusion: Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.
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- 2021
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4. Absence of PIK3CA mutation in primary mucinous ovarian carcinoma: An analysis of 20 Taiwanese cases by FemtoPath PIK3CA mutation screen kit
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Wan-Ru Chao, Yi-Ju Lee, and Chih-Ping Han
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Gynecology and obstetrics ,RG1-991 - Published
- 2022
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5. The Her2 gene aberrations in mucinous ovarian carcinoma: Analysis of twenty-one cases
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Hsiu-Hsiu Chiu, Wan-Ru Chao, Chi-Kuan Chen, Yi-Ju Lee, Ming-Yung Lee, and Chih-Ping Han
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Gynecology and obstetrics ,RG1-991 - Published
- 2020
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6. Mutation-free expression of c-Kit proto-oncogene in primary adenocarcinoma of uterine cervix
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Wan-Ru Chao, Chi-Kuan Chen, Lih-Min Han, and Chih-Ping Han
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Gynecology and obstetrics ,RG1-991 - Published
- 2016
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7. Assessment of HER2 Status Using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) Techniques in Mucinous Epithelial Ovarian Cancer: A Comprehensive Comparison between ToGA Biopsy Method and ToGA Surgical Specimen Method.
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Wan-Ru Chao, Ming-Yung Lee, Alexandra Ruan, Huang Pin Sheng, Jeng-Dong Hsu, Chih-Ping Han, and Chiew-Loon Koo
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Medicine ,Science - Abstract
We aimed to compare the assay performance characteristics of HER2 status in mucinous epithelial ovarian cancer (EOC) by ToGA (Trastuzumab for Gastric Cancer) biopsy versus ToGA surgical specimen methods. Forty-nine tissue microarray (TMA) samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using ToGA trial HER2 scoring methods. The overall concordance between IHC and FISH by the ToGA surgical specimen method is 97.56% and by the ToGA biopsy specimen method is 97.14%. The agreements of HER2 IHC results under both biopsy and surgical specimen methods were nearly perfect (weighted kappa = 0.845). Additionally, the percentage of Her2 FISH amplification showed increasing trend with increasing HER2 IHC ordinals (negative, equivocal, positive) by both TOGA biopsy (P
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- 2015
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8. Comparing the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma surgical specimen to the 2018 ASCO/CAP guideline for breast cancer in assessing the HER2 status in primary mucinous ovarian carcinoma
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Wan-Ru, Chao, Ming-Yung, Lee, Yi-Ju, Lee, Gwo-Tarng, Sheu, and Chih-Ping, Han
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Ovarian Neoplasms ,Receptor, ErbB-2 ,Breast Neoplasms ,Cell Biology ,General Medicine ,Carcinoma, Ovarian Epithelial ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,Pathology and Forensic Medicine ,Biomarkers, Tumor ,Humans ,Female ,Molecular Biology ,In Situ Hybridization, Fluorescence - Abstract
The successful experiences of HER2 inhibitors in patients with HER2 ( +) breast cancer (BC) and advanced gastroesophageal adenocarcinoma (GEA) have encouraged us to continuously explore the HER2 status and its potential as a therapeutic target in primary mucinous ovarian carcinoma (mOC). Using 49 primary mOC samples, we compared the assay characteristics of HER2 status between both 2017 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for GEA and 2018 ASCO/CAP for BC guideline recommendations. We demonstrated moderate to strong agreement between their HER2 IHC results (Weighted Kappa = 0.78) and perfect agreement between their HER2 FISH results (Kappa = 1.00). The overall concordance of non-equivocal HER2 IHC and HER2 FISH results was 97.56% (kappa = 0.93) by 2017 ASCO/CAP for GEA criteria and 100% (kappa = 1.00) by 2018 ASCO/CAP for BC criteria. The number (n = 8; 16.32%) of HER2 IHC equivocal (score + 2) by 2017 ASCO/CAP for GEA criteria was twofold higher than that (n = 4; 8.16%) by 2018 ASCO/CAP for BC criteria. Additionally, we identified one false-positive (FP) case (n = 1; 2.04%) that was HER2 IHC positive (score + 3), but HER2 FISH non-amplified result by the 2017 ASCO/CAP for GEA criteria. In conclusion, owing to the absence of FP/ FN and fewer equivocal cases of HER2 IHC, we recommend that the 2018 ASCO/CAP for BC are more appropriate than 2017 ASCO/CAP for GEA criteria in appraising the HER2 status in mOC and justifying the inclusion of eligible subjects for basket clinical trials of the newly developmental anti-HER2 treatments.
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- 2022
9. High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
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Ming-Yung Lee, Gwo-Tarng Sheu, Yi-Ju Lee, Chih-Ping Han, and Wan-Ru Chao
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Adult ,Proto-Oncogene Proteins B-raf ,Mutation rate ,endocrine system diseases ,medicine.medical_treatment ,Taiwan ,Carcinoma, Ovarian Epithelial ,medicine.disease_cause ,Targeted therapy ,Proto-Oncogene Proteins p21(ras) ,Mucinous ovarian carcinoma ,medicine ,Humans ,Missense mutation ,skin and connective tissue diseases ,neoplasms ,Mitogen-Activated Protein Kinase Kinases ,Ovarian Neoplasms ,BRAF gene ,business.industry ,MEK inhibitor ,Melanoma ,Obstetrics and Gynecology ,Gynecology and obstetrics ,medicine.disease ,Adenocarcinoma, Mucinous ,digestive system diseases ,enzymes and coenzymes (carbohydrates) ,Mutation ,Mutation (genetic algorithm) ,RG1-991 ,Cancer research ,Female ,KRAS ,Neoplasm Recurrence, Local ,business ,V600E - Abstract
Objective Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. Materials and methods 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Conclusion Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.
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- 2021
10. Both
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Chiew-Loon, Koo, Ming-Yung, Lee, Wan-Ru, Chao, and Chih-Ping, Han
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Ovarian Neoplasms ,Proto-Oncogene Proteins p21(ras) ,DNA Mutational Analysis ,Mutation ,Humans ,Female ,Carcinoma, Ovarian Epithelial ,Genes, erbB-2 ,Adenocarcinoma, Mucinous - Published
- 2022
11. Both Kras gene mutation and Her2 gene mutation tend to exist in an inverse manner but not mutually exclusive in mucinous ovarian carcinoma: An analysis of 21 taiwanese women
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Chih-Ping Han, Chiew-Loon Koo, Ming-Yung Lee, and Wan-Ru Chao
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Oncology ,Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2022
12. High frequency of BRAF mutations in mucinous ovarian carcinoma of Taiwanese patients
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Wan-Ru, Ming-Yung PhD Lee, Chao, Gwo-Tarng PhD Sheu, Yi-Ju Li, and Chih-Ping Han
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business.industry ,Ovarian carcinoma ,Cancer research ,Medicine ,business ,neoplasms ,digestive system diseases - Abstract
Background In view of the encouraging clinical evidence of BRAF inhibitors that can treat some melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. Methods DNA was extracted from micro-dissected tissue samples using the QIAamp® DNA FFPE Kit. The mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with subsequent Sanger sequencing method. Additionally, we extended our prior data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results Out of the 20 cases tested, 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n = 1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), dual T599I plus S602F (n = 1). The BRAF missense mutation (S602F) is novel. In addition, the prevalence of BRAF gene mutation is significantly higher than HER2 gene mutation (80% vs. 35%; p = 0.022,) and HER2 gene amplification (80% vs. 35%; p = 0.022), respectively. However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Discussion Our results showed that BRAF mutation is not uncommon in primary MOC of Taiwanese. When taken together with previous published data, we found that the activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive, but simultaneously independent. However, they may even have a synergistic effect in tumorigenesis. Conclusions The BRAF variant with T599I stands the majority. These findings suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor in MOC. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage MOC patients carrying each class of BRAF mutation.
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- 2020
13. Association of Fibroblast Growth Factor Receptor 4 Genetic Polymorphisms With the Development of Uterine Cervical Cancer and Patient Prognosis
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Tze-Ho Chen, Wea-Lung Lin, Chih-Ping Han, Shun-Fa Yang, Yu-Fan Liu, and Po-Hui Wang
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Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Genotype ,Mutant ,Fibroblast Growth Factor 4 ,Taiwan ,Uterine Cervical Neoplasms ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,law ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genotyping ,Alleles ,Polymerase chain reaction ,Aged ,business.industry ,Obstetrics and Gynecology ,Fibroblast growth factor receptor 4 ,Middle Aged ,Prognosis ,Genotype frequency ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,business - Abstract
This is the first study to investigate the relationships among fibroblast growth factor receptor 4 (FGFR4) genetic polymorphisms, development of uterine cervical cancer, clinicopathological variables, and patient prognosis in Taiwanese women. Real-time polymerase chain reaction and genotyping were used to detect the genotype frequencies of 4 FGFR4 single-nucleotide polymorphisms (SNPs), rs351855 (C/T, Gly388Arg), rs2011077 (G/A), rs7708357 (G/A), and rs1966265 (Ile10Val), in 138 patients with invasive cancer, 89 with precancerous lesions of uterine cervix, and 335 normal controls. The results showed that there is no significant difference in the frequencies of FGFR4 SNPs rs351855, rs2011077, rs7708357, and 1966265 between women with cervical invasive cancer and normal controls even after controlling for age. However, significant differences existed in the distributions of the FGFR4 genetic polymorphism rs2011077, when mutant homozygotes (AA) were compared using other genotypes (GG/GA) as a reference, as well as rs1966265, when mutant homozygotes (AA) were compared using GG/GA as a reference, between women with cervical precancerous lesions and normal women even after controlling for age. In multivariate analysis, lymph node metastasis was associated with cancer recurrence, and lymph node metastasis and FGFR4 rs351855 were associated with patient survival. In conclusion, our study demonstrated that FGFR4 rs2011077 and rs1966265 are associated with the progression of cervical normal tissues to precancerous lesions in Taiwanese women. Moreover, rs351855 (Gly388Arg) is the only FGFR4 genetic polymorphism that is associated with patient survival.
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- 2018
14. The Her2 gene aberrations in mucinous ovarian carcinoma: Analysis of twenty-one cases
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Chih-Ping Han, Chi-Kuan Chen, Ming-Yung Lee, Yi-Ju Lee, Hsiu-Hsiu Chiu, and Wan-Ru Chao
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Ovarian Neoplasms ,business.industry ,Obstetrics and Gynecology ,Genes, erbB-2 ,Adenocarcinoma, Mucinous ,lcsh:Gynecology and obstetrics ,Text mining ,Ovarian carcinoma ,Mutation ,Cancer research ,Medicine ,Humans ,Female ,business ,Gene ,lcsh:RG1-991 - Published
- 2020
15. Molecular profiling of c-KIT oncogene in high grade neuroendocrine carcinoma of the uterine cervix: Analysis of twelve cases
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Wen-Chih Tsai, Chih-Ping Han, Chi-Kuan Chen, and Wan-Ru Chao
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Neoplasm Grading ,business.industry ,DNA Mutational Analysis ,Obstetrics and Gynecology ,Gene Expression ,Uterine Cervical Neoplasms ,medicine.disease ,Carcinoma, Neuroendocrine ,Proto-Oncogene Proteins c-kit ,Uterine cervix ,Gene expression ,Cancer research ,Carcinoma ,Medicine ,Humans ,Neuroendocrine carcinoma ,Female ,business ,Kit oncogene - Published
- 2018
16. The status of Her2 amplification and Kras mutations in mucinous ovarian carcinoma
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Chih-Ping Han, Wan-Ru Chao, Kuang-Leei Chang, and Ming-Yung Lee
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0301 basic medicine ,endocrine system diseases ,Genes, BRCA2 ,Genes, BRCA1 ,Angiogenesis Inhibitors ,Carcinoma, Ovarian Epithelial ,medicine.disease_cause ,Kras mutation ,0302 clinical medicine ,Mucinous ovarian carcinoma ,Ovarian carcinoma ,Drug Discovery ,HER2 Amplification ,Neoplasm Metastasis ,skin and connective tissue diseases ,Letter to the Editor ,Early Detection of Cancer ,Ovarian Neoplasms ,Hybridization probe ,Her2 amplification ,Middle Aged ,Prognosis ,Adenocarcinoma, Mucinous ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,KRAS ,Mucinous cystadenocarcinoma ,Hormone Replacement Therapy ,Antineoplastic Agents ,Poly(ADP-ribose) Polymerase Inhibitors ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Molecular Biology ,neoplasms ,Germ-Line Mutation ,business.industry ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Mutation ,Cancer research ,Neoplasm Recurrence, Local ,Ovarian cancer ,business ,Forecasting - Abstract
Epithelial ovarian cancer is the commonest cause of gynaecological cancer-associated death. The disease typically presents in postmenopausal women, with a few months of abdominal pain and distension. Most women have advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III), for which the standard of care remains surgery and platinum-based cytotoxic chemotherapy. Although this treatment can be curative for most patients with early stage disease, most women with advanced disease will develop many episodes of recurrent disease with progressively shorter disease-free intervals. These episodes culminate in chemoresistance and ultimately bowel obstruction, the most frequent cause of death. For women whose disease continues to respond to platinum-based drugs, the disease can often be controlled for 5 years or more. Targeted treatments such as antiangiogenic drugs or poly (ADP-ribose) polymerase inhibitors offer potential for improved survival. The efficacy of screening, designed to detect the disease at an earlier and curable stage remains unproven, with key results expected in 2015.
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- 2016
17. Association of single-nucleotide polymorphisms of high-mobility group box 1 with susceptibility and clinicopathological characteristics of uterine cervical neoplasia in Taiwanese women
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Hsin-Hung Wu, Shun-Fa Yang, Chih-Ping Han, Hsiang-Ling Wang, Shiuan-Chih Chen, Yu-Fan Liu, Long-Yau Lin, Po-Hui Wang, and Wea-Lung Lin
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0301 basic medicine ,Gynecology ,Cervical cancer ,medicine.medical_specialty ,business.industry ,Cancer ,Single-nucleotide polymorphism ,General Medicine ,Odds ratio ,medicine.disease ,Gastroenterology ,law.invention ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,High-mobility group ,law ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,SNP ,business ,Genotyping ,Polymerase chain reaction - Abstract
To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12–3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24–3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22–3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22–3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.
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- 2016
18. Single-Nucleotide Polymorphisms and Haplotypes of Membrane Type 1-Matrix Metalloproteinase in Susceptibility and Clinical Significance of Squamous Cell Neoplasia of Uterine Cervix in Taiwan Women
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Jinghua Tsai Chang, Shun-Fa Yang, Chih-Ping Han, Po-Hui Wang, Yi-Torng Tee, Chiung-Ling Liao, Shiuan-Chih Chen, and Yu-Fan Liu
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Adult ,Cervical cancer ,Haplotype ,Taiwan ,Uterine Cervical Neoplasms ,Obstetrics and Gynecology ,Single-nucleotide polymorphism ,Middle Aged ,Biology ,medicine.disease ,Polymorphism, Single Nucleotide ,Molecular biology ,Exon ,Haplotypes ,Dysplasia ,Genotype ,Matrix Metalloproteinase 14 ,medicine ,Humans ,SNP ,Female ,Genetic Predisposition to Disease ,Neoplasms, Squamous Cell ,Genotyping - Abstract
Membrane type 1-matrix metalloproteinase (MT1-MMP) participates in the activity of MMP-2, which correlates with cancer of uterine cervix. Single-nucleotide polymorphisms (SNPs) in promoter and exon of MT1-MMP may influence their binding with transcription factors and gene transcription. To date, no study reports the association of the MT1-MMP polymorphisms with cervical neoplasia. Therefore, we investigated the influence of the MT1-MMP gene polymorphisms on the susceptibility and clinicopathological variables of cervical neoplasia for women in Taiwan. We recruited 72 patients with cervical squamous cell carcinoma and 63 with high-grade dysplasia as 1 subgroup. Meanwhile, 280 control women were included as another subgroup. The SNPs rs1003349 (site -165), rs2236307 (+7096), and rs3751489 (+8153) as well as rs2236302 (site +6727) of MT1-MMP gene were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time PCR genotyping, respectively. Then, we correlated these SNPs and haplotypes with the development of cervical neoplasia and cancer clinicopathological variables. We found that women with CC genotype in rs2236307 SNP exhibited a more risk to develop cervical neoplasia as compared with those with wild genotype TT. Haplotypes -165 T, +6727 C, +7096 C, +8153 G or -165 G, +6727 G, +7096 T, and +8153 G and diplotypes including at least 1 type of these haplotypes of MT1-MMP gene showed a higher risk of cervical neoplasia. However, both haplotypes were not significantly correlated with the clinicopathological characteristics of cervical cancer. In conclusion, Taiwan women with variant homozygote CC (+7096) and haplotypes, TCCG and GGTG, of MT1-MMP exhibit more risk in developing cervical neoplasia.
- Published
- 2012
19. Significant Association of Elevated Concentration of Plasma YKL-40 with Disease Severity in Patients With Pelvic Inflammatory Disease
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Shu-Hsin Lee, Chih-Ping Han, Shun-Fa Yang, Long-Yau Lin, Jinghua Tsai Chang, Ching-Yi Lin, Meng-Chih Lee, Po-Hui Wang, and Maw-Sheng Lee
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musculoskeletal diseases ,Microbiology (medical) ,medicine.medical_specialty ,business.industry ,Biochemistry (medical) ,Clinical Biochemistry ,Significant difference ,Public Health, Environmental and Occupational Health ,Hematology ,Disease ,medicine.disease ,Gastroenterology ,Surgery ,Medical Laboratory Technology ,medicine.anatomical_structure ,Disease severity ,White blood cell ,Internal medicine ,Pelvic inflammatory disease ,medicine ,Immunology and Allergy ,Biomarker (medicine) ,In patient ,Abscess ,business - Abstract
Introduction To date, no study reports the implication of YKL-40 in pelvic inflammatory disease (PID). Therefore, we investigate the levels of plasma YKL-40 in patients with PID and further associate its expression with the severity of disease. Methods We designed a hospital-based case-control study with approximate 1:1 ratio and consecutively recruited 64 patients with PID and 70 control women. We collected blood samples from 64 women with PID before and after they received treatment and 70 control women to detect levels of plasma YKL-40 and C-reactive protein (CRP) as well as white blood cell and neutrophil counts. Results The results revealed that levels of plasma YKL-40 were significantly elevated in patients with PID as compared to those in controls (38.36 vs. 21.69 ng/ml, P = 0.001) but the significant difference was restricted to women aged 30 years or old after age stratification (56.75 vs. 23.61 ng/ml, P ≤ 0.001). It declined significantly after they received treatment (median: 38.36 vs. 27.54 ng/ml; P ≤ 0.001). Although both plasma YKL-40 and CRP were elevated in patients with tubo-ovarian abscess, PID patients with surgery exhibited higher YKL-40 concentration than those without surgery (median: 82.05 vs. 30.19 ng/ml, P = 0.005) and only plasma YKL-40 was significantly associated with the length of the hospital stay (P ≤ 0.001, R = 0.604). Conclusion We conclude that once individuals are diagnosed to have PID, YKL-40 may act as a biomarker to predict the severity and clinical outcome of the disease. J. Clin. Lab. Anal. 26:136-142, 2012. © 2012 Wiley Periodicals, Inc.
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- 2012
20. A promising hypothesis of c-KIT methylation/ expression paradox in c-KIT (+) squamous cell carcinoma of uterine cervix ----- CTCF transcriptional repressor regulates c-KIT proto-oncogene expression
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Alexandra Ruan, Po-Hui Wang, Shih-Wen Chang, Jau-Chen Lin, Chih-Ping Han, and Wan-Ru Chao
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Histology ,Uterine Cervical Neoplasms ,Repressor ,Biology ,Proto-Oncogene Mas ,Epigenesis, Genetic ,Pathology and Forensic Medicine ,c-KIT proto-oncogene ,Animals ,Humans ,Epigenetics ,Regulation of gene expression ,Squamous cell carcinoma of uterine cervix ,General Medicine ,Methylation ,Hypothesis ,DNA Methylation ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Proto-Oncogene Proteins c-kit ,CpG site ,CTCF ,DNA methylation ,Carcinoma, Squamous Cell ,Cancer research ,CTCF repressor ,Female - Abstract
We recently reported one interesting case showing mutation-free c-KIT proto-oncogene overexpression and paradoxical hypermethylation in 54 cases of primary squamous cell carcinoma of uterine cervix (SCC). However, its molecular mechanisms still remain unknown. We propose the hypothesis that increased methylation at the CpG islands on the promoter near the first exon region might interfere with the binding of CTCF repressor with c-KIT promoter that regulates c-KIT proto-oncogene expression in such case. Further studies focusing on the status of epigenetic modifications of mutation-free c-KIT (+) tumors are encouraged.
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- 2015
21. Identification of the Coexisting HER2 Gene Amplification and Novel Mutations in the HER2 Protein-Overexpressed Mucinous Epithelial Ovarian Cancer
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Jeng-Dong Hsu, Ming-Yung Lee, Wu-Hsien Kuo, Yeu-Sheng Tyan, Hung Chiang, Wea-Lung Lin, Alexandra Ruan, Fong-Lin Chen, and Chih-Ping Han
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endocrine system diseases ,Receptor, ErbB-2 ,Biology ,Polymerase Chain Reaction ,Immunoenzyme Techniques ,Germline mutation ,Surgical oncology ,Humans ,Epithelial ovarian cancer ,skin and connective tissue diseases ,Gene ,In Situ Hybridization, Fluorescence ,Ovarian Neoplasms ,Gene Amplification ,DNA, Neoplasm ,Prognosis ,Adenocarcinoma, Mucinous ,Molecular biology ,female genital diseases and pregnancy complications ,Cystadenocarcinoma, Serous ,Endometrial Neoplasms ,Survival Rate ,Oncology ,Mutation ,HER2 Gene Amplification ,Cancer research ,Female ,Surgery ,Adenocarcinoma, Clear Cell - Abstract
Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC).Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing.The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases.HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy.
- Published
- 2011
22. The HER2 gene copies per tumor cell either before or after correction for chromosome-17 correlated significantly with HER2 IHC results in epithelial ovarian cancer in a tissue microarray study
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Shao-Chuan Wang, Wea-Lung Lin, Yi-Ju Li, Wen-Chih Tsai, Alexandra Ruan, Po-Hui Wang, Ming-Yung Lee, Fong-Lin Chen, Chih-Ping Han, and Hung Chiang
- Subjects
Receptor, ErbB-2 ,Gene Dosage ,Statistics, Nonparametric ,Breast cancer ,medicine ,Humans ,skin and connective tissue diseases ,neoplasms ,Gene ,In Situ Hybridization, Fluorescence ,Ovarian Neoplasms ,Tissue microarray ,biology ,medicine.diagnostic_test ,Hybridization probe ,Gene Amplification ,Obstetrics and Gynecology ,General Medicine ,Genes, erbB-2 ,Microarray Analysis ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Chromosome 17 (human) ,biology.protein ,Cancer research ,Female ,Antibody ,Chromosomes, Human, Pair 17 ,Fluorescence in situ hybridization - Abstract
HER2 gene amplification and HER2 protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast cancer patients. The purpose of this study is to evaluate the correlation between HER2 protein expressions and the HER2 gene copies per tumor cell either before or after chromosome-17 correction in epithelial ovarian cancer (EOC). Adopting 2007 ASCO/CAP guideline recommendations for HER2 testing, 27 tissue microarray (TMA) samples from EOC patients were analyzed by immunohistochemistry (IHC) using Dako, c-erb-B2 antibody and subsequently examined by fluorescence in situ hybridization (FISH) using Abbott/Vysis, PathVysion HER2 DNA Probe Kit. The overall concordance revealed 81.5% between HER2 IHC and HER2 FISH results. Additionally, HER2 gene copies prior to chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P = 0.026), as did the HER2 gene copies after chromosome-17 correction (P = 0.028). On the other hand, HER2 IHC results correlated significantly with both chromosome-17 uncorrected HER2 gene copy numbers (ρ = 0.430, P = 0.025) and chromosome-17 corrected HER2 gene copy numbers (ρ = 0.524, P = 0.027). We demonstrated that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC result categories; and tests for the HER2 gene copies per tumor cell either before or after correction for chromosome-17 can be applied as a potentially valuable tool in analyzing the HER2 status in EOC.
- Published
- 2010
23. Polymorphisms of Human Nonmetastatic Clone 23 Type 1 Gene and Neoplastic Lesions of Uterine Cervix
- Author
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Jiunn-Liang Ko, Po Hui Wang, Long Yau Lin, Ching Yi Lin, Hsiu Ting Tsai, Chi Yen Feng, Yu-Fan Liu, Chih Ping Han, Shun-Fa Yang, Shiuan Chih Chen, Jia Sin Yang, and Yi Torng Tee
- Subjects
Pathology ,medicine.medical_specialty ,Genotype ,Taiwan ,Clone (cell biology) ,Uterine Cervical Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Loss of heterozygosity ,Genetic variation ,medicine ,Humans ,SNP ,Gene ,Chi-Square Distribution ,Genetic Variation ,Obstetrics and Gynecology ,Cancer ,DNA, Neoplasm ,Middle Aged ,NM23 Nucleoside Diphosphate Kinases ,medicine.disease ,Cancer research ,Female - Abstract
Single-nucleotide polymorphisms (SNP) in promoter of human nonmetastatic clone 23 type 1 (nm23-H1) may affect their binding with transcription factors and affect promoter activity as well as gene transcription. Therefore, we investigated the impact of the nm23-H1 gene polymorphisms on the neoplastic lesions of uterine cervix in mid-Taiwan women (women who live in the central area of Taiwan). We expected that women with different genotypes in nm23-H1 polymorphisms, such as rs34214448, rs16949649, or rs2302254, may have different incidences of cervical neoplasia.In total, 366 blood samples were collected from 244 healthy women and 122 patients with cervical neoplasia to analyze 3 nm23-H1 gene single-nucleotide polymorphisms (rs34214448, rs16949649, and rs2302254).The heterozygous genotypes, TG in rs34214448 or TC in rs16949649, were differentially distributed between patients with cervical neoplasia and normal women (Hommel adjusted P = .0440 and .0435, respectively) as compared to their homozygotes. Moreover, compared to those with wild-type homozygotes and heterozygotes, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exert different distributions between patients with cervical neoplasia and normal women (P = .058 and .058). Interestingly, we found the genotype distribution of rs34214448 has significant association with that of rs16949649 with high consistency.Mid-Taiwan women with the polymorphic heterozygotes TG in rs34214448 or TC in rs16949649 of human nonmetastatic clone 23 type 1 promoter have the tendency to develop cervical neoplasia while compared to their homozygous counterparts. However, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exhibit less tendency as compared to those with wild-type homozygotes and heterozygotes.
- Published
- 2010
24. Assessment of Common Bile Duct Using Laparoscopic Ultrasound During Laparoscopic Cholecystectomy
- Author
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Lu Chang Ho, Chung Chin Yao, Han Ming Chen, Ya Wen Cheng, Chun-Che Lin, Chih Ping Han, Shih Wen Chang, and Shing Moo Huang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Gallstones ,digestive system ,Endosonography ,Intermediate group ,medicine ,Humans ,Laparoscopic cholecystectomy ,Aged ,Common Bile Duct ,Common bile duct ,Bile duct ,business.industry ,General surgery ,Echogenicity ,Laparoscopic ultrasound ,Middle Aged ,medicine.disease ,Acoustic shadow ,digestive system diseases ,medicine.anatomical_structure ,Cholecystectomy, Laparoscopic ,Feasibility Studies ,Female ,Surgery ,Radiology ,business - Abstract
BACKGROUND: Several reports have shown that laparoscopic ultrasound (LUS) examination of the bile duct is promising and suggest it as a primary method for bile duct imaging during laparoscopic cholecystectomy (LC). This study was designed to evaluate the feasibility of LUS during LC, and the occurrence rate of common bile duct (CBD) stones during LC. MATERIALS AND METHODS: One hundred and fifteen consecutive patients with gallstones were enrolled into this study. LUS was used to assess the CBD routinely during LC, which was successfully performed in 112 cases. Choledocholithiasis was rated before LC as being of low, intermediate, or high probability on the basis of clinical, laboratory, and/or imaging findings (Cotton criteria). Duct calculi were defined as echogenic material within the CBD, which cast discrete acoustic shadows. Sludge was defined as mobile or floating low-amplitude echogenic material without discrete acoustic shadowing. RESULTS: The CBD could be evaluated in 112 of 115 LC (97.4%) patients (72 females and 40 males). The mean age was 54+/-16 years old. The occurrence rate of CBD stones in the low-risk group was 7%, that in the intermediate group was 36.4%, and the high-risk group was 78.9%. The overall incidence of CBD stones was 25.0%. CONCLUSIONS: With increasing experience, LUS can become the routine method for evaluating the bile duct during LC. A more aggressive preoperative evaluation of CBD is mandated in the intermediate and high-risk groups of patients suspected of having CBD stones.
- Published
- 2009
25. Five commonly used markers (p53, TTF1, CK7, CK20, and CK34βE12) are of no use in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study
- Author
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Chiew Loon Koo, Alexandra Ruan, Yeu Sheng Tyan, Chih Ping Han, Ya Wen Cheng, Lai Fong Kok, Po Hui Wang, Ming-Yung Lee, and Tina S. Wu
- Subjects
Pathology ,medicine.medical_specialty ,medicine.drug_class ,Uterine Cervical Neoplasms ,Keratin-20 ,Diagnostic dilemma ,Adenocarcinoma ,Monoclonal antibody ,Statistics, Nonparametric ,Biomarkers, Tumor ,medicine ,Humans ,Retrospective Studies ,Site of origin ,Tissue microarray ,business.industry ,Extension study ,Keratin-7 ,Antibodies, Monoclonal ,Obstetrics and Gynecology ,General Medicine ,Immunohistochemistry ,Endometrial Neoplasms ,DNA-Binding Proteins ,Female ,Tumor Suppressor Protein p53 ,business ,Transcription Factors - Abstract
The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depends on the tumor's site of origin. Some panels of antibodies help to distinguish primary ECA from EMA. However, unexpected expressions of those markers often exist, which causes this diagnostic dilemma to be still unresolved. In this study, we investigate five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) to evaluate their potential use in distinguishing between these two gynecologic malignancies.A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were immunostained with the five aforementioned commercially available antibodies.Immunohistochemical (IHC) expressions of p53, TTF1, CK7, CK20, and CK34betaE12 were all nonsignificant (P0.05) in frequency differences between the immunostaining results (positive vs. negative) in tumors from both the two primary adenocarcinomas (ECA vs. EMA).It is still uncertain which markers or panels would be the most appropriate for making diagnoses; hence, exploration of other useful markers, which make a definitive distinction between ECA and EMA merits further studies. This study, however, uncovered that the five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) are of no beneficial value in distinguishing between primary ECA and EMA.
- Published
- 2009
26. Comparing the scoring mechanisms of p16INK4a immunohistochemistry based on independent nucleic stains and independent cytoplasmic stains in distinguishing between endocervical and endometrial adenocarcinomas in a tissue microarray study
- Author
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Ming-Yung Lee, Mei Fen Kung, Yeu Sheng Tyan, Lai Fong Kok, Chih Ping Han, Tina S. Wu, Ya Wen Cheng, and Po Hui Wang
- Subjects
Cytoplasm ,Pathology ,medicine.medical_specialty ,Uterus ,Uterine Cervical Neoplasms ,Adenocarcinoma ,Biology ,Sensitivity and Specificity ,Stain ,Statistics, Nonparametric ,Antigen ,Predictive Value of Tests ,medicine ,Humans ,Clinical significance ,Cyclin-Dependent Kinase Inhibitor p16 ,Retrospective Studies ,Cell Nucleus ,Tissue microarray ,Reproducibility of Results ,Obstetrics and Gynecology ,General Medicine ,Immunohistochemistry ,Molecular biology ,Endometrial Neoplasms ,Staining ,medicine.anatomical_structure ,Nucleic acid ,Female - Abstract
Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect the uterus; however, their biological behaviors are quite different. This distinction has clinical significance because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate two different scoring mechanisms of p16INK4a immunohistochemical (IHC) stain in distinguishing between primary ECAs and EMAs. A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 21 EMAs. Tissue array sections were stained with a commercially available antibody, p16INK4a. The avidin–biotin complex method was used to visualize antigens. The staining intensity and extent of the IHC reactions were evaluated using a semi-quantitative scoring system. Two scoring methods were defined on the following bases: (1) independent cytoplasmic staining alone, irrespective of nucleic stain (Method C) and (2) independent nucleic staining alone, irrespective of cytoplasmic staining. (Method N). Of the two scoring mechanisms for p16INK4a expression, Method N showed a significant difference (P = 0.015), but Method C showed no significant (P = 0.432) frequency differences in distinguishing between ECAs and EMAs. However, Method N had a higher overall accuracy rate (71.4%) in accurately diagnosing ECAs from EMAs in the total number of p16INK4a IHC cases. According to the data of p16INK4a expression in this TMA study, Method N is favorable and efficient in distinguishing between ECAs and EMAs, while Method C is not.
- Published
- 2009
27. Evaluation of Matrix Metalloproteinase—2 Expression in Cervical Carcinogenesis Using Tissue Array and Integrated Optical Density for Immunoreactivity
- Author
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Shun-Fa Yang, Shiuan-Chih Chen, Long-Yau Lin, Horng-Jyh Tsai, Chih-Ping Han, Yi-Torng Tee, Jiunn-Liang Ko, Po-Hui Wang, and Gin-Den Chen
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Gelatinase A ,Uterine Cervical Neoplasms ,Matrix (biology) ,Matrix metalloproteinase ,Cervical intraepithelial neoplasia ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,neoplasms ,Cervical cancer ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Uterine Cervical Dysplasia ,medicine.disease ,030104 developmental biology ,Epidermoid carcinoma ,Tissue Array Analysis ,High Grade Cervical Intraepithelial Neoplasia ,Carcinoma, Squamous Cell ,Matrix Metalloproteinase 2 ,Female ,business ,Carcinogenesis - Abstract
To correlate matrix metalloproteinase-2 (MMP-2) expression with cervical carcinogenesis, the authors use reverse-transcription polymerase chain reaction to detect MMP-2 mRNA expression in 10 cervical squamous cell carcinoma (SCC), 10 high-grade cervical intraepithelial neoplasia (CIN), and 10 normal tissues. They further detect MMP-2 immunoreactivity of 24 tissue cores in each SCC, high-and low-grade CINs, and a healthy subgroup on a tissue array using integrated optical density (IOD) for number and intensity of stained cells in 345 x 345 pixels. They found the mRNA expression of MMP-2 to be higher in most SCCs (9/10 samples) and high-grade CINs (7/10 samples) but lower in normal tissues. The IOD of MMP-2 was significantly higher in high-grade CIN than in normal and low-grade CIN tissue cores (P.001 for both) and significantly higher in SCC than in high-grade CIN tissue cores (P.001). The results show that MMP-2 upregulation confers on tumor cells the ability to degrade the subepithelial basement membrane and subsequently invade the cervix.
- Published
- 2007
28. Human Nonmetastatic Clone 23 Type 1 Gene Suppresses Migration of Cervical Cancer Cells and Enhances the Migration Inhibition of Fungal Immunomodulatory Protein From Ganoderma tsugae
- Author
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Jiunn-Liang Ko, Gin-Den Chen, Long-Yau Lin, Chih-Ping Han, Po-Hui Wang, Shun-Fa Yang, and Shiuan-Chih Chen
- Subjects
0301 basic medicine ,Ganoderma ,Clone (cell biology) ,Uterine Cervical Neoplasms ,Motility ,Matrix metalloproteinase ,Transfection ,Fungal Proteins ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Ganoderma tsugae ,Humans ,Immunologic Factors ,Gene ,030219 obstetrics & reproductive medicine ,biology ,Obstetrics and Gynecology ,Cell migration ,NM23 Nucleoside Diphosphate Kinases ,biology.organism_classification ,030104 developmental biology ,Cell Migration Inhibition ,Immunology ,Cancer research ,Female ,HeLa Cells - Abstract
The authors investigate the effects of human nonmetastatic clone 23 type 1 (nm23-H1 ) gene and fungal immunomodulatory protein-Ganoderma tsugae (FIP-gts) on the metastatic potential of cervical cancer cells and assess whether nm23-H1 can influence the action of FIP-gts using cell migration and invasion assays and gelatin zymography. The nm23-H1 gene was stably transfected into Caski cells, which lacked nm23-H1 expression. The results show that nm23-H1 stably transfected Caski cells exhibit reduced cell migration but no change of cell invasion and matrix metalloproteinase (MMP)-2 and -9 activities. FIP-gts reduced cell migration in SiHa and nm23-H1 transfected Caski cells more significantly compared with Caski cells and reduced invasion in Caski and nm23-H1-transfected Caski cells, but it exerted no influence on MMP-2 and MMP-9 activities in them. Conclusively, the nm23-H1 gene suppresses cervical cancer cell migration but not invasion and activities of MMP-2 and MMP-9 and enhances the inhibition of FIP-gts upon migration.
- Published
- 2007
29. Assessment of HER2 Status Using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) Techniques in Mucinous Epithelial Ovarian Cancer: A Comprehensive Comparison between ToGA Biopsy Method and ToGA Surgical Specimen Method
- Author
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Chih-Ping Han, Huang Pin Sheng, Ming-Yung Lee, Chiew-Loon Koo, Alexandra Ruan, Wan-Ru Chao, and Jeng-Dong Hsu
- Subjects
Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Biopsy ,Gene Dosage ,lcsh:Medicine ,Carcinoma, Ovarian Epithelial ,Specimen Handling ,Breast cancer ,Surgical oncology ,Carcinoma ,medicine ,Humans ,Neoplasms, Glandular and Epithelial ,lcsh:Science ,In Situ Hybridization, Fluorescence ,Ovarian Neoplasms ,Multidisciplinary ,Tissue microarray ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Ovary ,Gene Amplification ,Cancer ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,lcsh:Q ,Female ,business ,Fluorescence in situ hybridization ,Research Article - Abstract
We aimed to compare the assay performance characteristics of HER2 status in mucinous epithelial ovarian cancer (EOC) by ToGA (Trastuzumab for Gastric Cancer) biopsy versus ToGA surgical specimen methods. Forty-nine tissue microarray (TMA) samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using ToGA trial HER2 scoring methods. The overall concordance between IHC and FISH by the ToGA surgical specimen method is 97.56% and by the ToGA biopsy specimen method is 97.14%. The agreements of HER2 IHC results under both biopsy and surgical specimen methods were nearly perfect (weighted kappa = 0.845). Additionally, the percentage of Her2 FISH amplification showed increasing trend with increasing HER2 IHC ordinals (negative, equivocal, positive) by both TOGA biopsy (P
- Published
- 2015
30. A Qualitative Study Comparing the Assay Performance Characteristics Between the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists HER2 Scoring Methods in Mucinous Epithelial Ovarian Cancer
- Author
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Chi-Kuan Chen, Wan-Ru Chao, Ming-Yung Lee, Yu-Ting Wang, Wea-Lung Lin, Cheng-Ping Yu, and Chih-Ping Han
- Subjects
Oncology ,medicine.medical_specialty ,Concordance ,Article ,Trastuzumab ,Internal medicine ,Quality Improvement Study ,medicine ,Humans ,skin and connective tissue diseases ,In Situ Hybridization, Fluorescence ,Gynecology ,Ovarian Neoplasms ,Tissue microarray ,medicine.diagnostic_test ,business.industry ,Process Assessment, Health Care ,Scoring methods ,Cancer ,General Medicine ,Genes, erbB-2 ,medicine.disease ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,Quality Improvement ,Female ,business ,Kappa ,Algorithms ,medicine.drug ,Fluorescence in situ hybridization - Abstract
The remarkable success of trastuzumab and other newly developed anti-HER2 (human epidermal growth factor receptor 2) therapies in breast, gastric, or gastroesophageal junction cancer patients has supported us to investigate the HER2 status and its possible therapeutic implication in mucinous epithelial ovarian cancer (EOC). However, there is currently no standardization of HER2 scoring criteria in mucinous EOC. In this study, we aimed to compare both the assay performance characteristics of the 2007 and the 2013 American Society for Clinical Oncology and College of American Pathologists scoring methods. Forty-nine tissue microarray samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using the 2007 and the 2013 criteria, respectively. The overall concordance between IHC and FISH by the 2007 criteria was 97.92 % (kappa = 0.921), and that by the 2013 criteria was 100% (kappa = 1.000). The percentage of Her2 FISH-amplified cases showed an increasing trend significantly through their corresponding HER2 IHC ordinals by the 2007 and the 2013 criteria, respectively (P
- Published
- 2014
31. Unusual c-KIT+ squamous cell carcinoma of the uterine cervix showing paradoxical hypermethylation of the c-KIT proto-oncogene
- Author
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Jau-Chen Lin, Chih-Ping Han, Wan-Ru Chao, Chi-Kuan Chen, Lih-Min Han, and Wea-Lung Lin
- Subjects
Oncology ,medicine.medical_specialty ,Oncogene ,business.industry ,Obstetrics and Gynecology ,Uterine Cervical Neoplasms ,Cervix Uteri ,DNA Methylation ,medicine.disease ,Proto-Oncogene Mas ,Proto-Oncogene Proteins c-kit ,Uterine cervix ,Reproductive Medicine ,Internal medicine ,DNA methylation ,Cancer research ,medicine ,Carcinoma ,Carcinoma, Squamous Cell ,Humans ,Basal cell ,Female ,business - Published
- 2014
32. Unusual c-KIT (+) squamous cell carcinoma of uterine cervix showing remarkable platelet-derived growth factor receptor, alpha subunit expression, but no activating mutation
- Author
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Po-Hui Wang, Hung Chiang, Chi-Kuan Chen, Chih-Ping Han, and Chih-Kung Lin
- Subjects
medicine.medical_specialty ,Histology ,Protein subunit ,Platelet-Derived Growth Factor Receptor Alpha ,General Medicine ,Biology ,Activating mutation ,Pathology and Forensic Medicine ,Endocrinology ,Uterine cervix ,Internal medicine ,medicine ,Cancer research ,Basal cell - Published
- 2011
33. Overexpression of c-KIT (CD117) occurs infrequently in squamous cell carcinoma of the uterine cervix
- Author
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Alexandra Ruan, Jang-Fang Kuo, Ming-Yung Lee, Po-Hui Wang, Chi-Kuan Chen, Shun-Fa Yang, Hung Chiang, Wea-Long Lin, Chih-Ping Han, and James S. Lewis
- Subjects
Pathology ,medicine.medical_specialty ,Histology ,Uterine Cervix Squamous Cell Carcinoma ,Kit gene ,Cancer ,Anatomical pathology ,General Medicine ,Biology ,medicine.disease ,Pathology and Forensic Medicine ,C kit cd117 ,Uterine cervix ,Carcinoma ,medicine ,Basal cell - Published
- 2011
34. Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of the 2013 ASCO/CAP guideline update
- Author
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Wan-Ru Chao, Chih-Ping Han, Gwo-Tarng Sheu, Chiew-Loon Koo, Wea-Lung Lin, and Ming-Yung Lee
- Subjects
Oncology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Concordance ,Biopsy ,Taiwan ,Carcinoma, Ovarian Epithelial ,White People ,Pathology and Forensic Medicine ,Asian People ,Predictive Value of Tests ,Internal medicine ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Neoplasms, Glandular and Epithelial ,skin and connective tissue diseases ,neoplasms ,In Situ Hybridization, Fluorescence ,Societies, Medical ,Ovarian Neoplasms ,Tissue microarray ,medicine.diagnostic_test ,business.industry ,Gene Amplification ,Cancer ,Guideline ,medicine.disease ,Prognosis ,Immunohistochemistry ,Phenotype ,Predictive value of tests ,Practice Guidelines as Topic ,Surgery ,Female ,Guideline Adherence ,Anatomy ,business ,Neoplasms, Cystic, Mucinous, and Serous ,Fluorescence in situ hybridization ,Chromosomes, Human, Pair 17 - Abstract
Her2 gene amplification and protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast, gastric, or gastro-esophageal junction cancer patients. The purpose of this study was to evaluate the HER2 status in the mucinous epithelial ovarian cancer (EOC). Adopting the 2013 American Society for Clinical Oncology and the College of American Pathologists guideline update for HER2 testing, 49 tissue microarray samples of mucinous EOC were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests. The prevalence of HER2 positivity in Asian mucinous EOC was 9 of 49 Asian women (18.37%). The overall concordance was 100% between IHC and FISH results. Her2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P
- Published
- 2014
35. Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix
- Author
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Shiuan Chih Chen, Chih Ping Han, Yu Wen Lin, Chih Hsien Wu, Ti Yuan Yang, Po Hui Wang, Jiunn-Liang Ko, and Ming Hsien Chien
- Subjects
3-Hydroxysteroid Dehydrogenases ,Uterine Cervical Neoplasms ,Lipocalin ,Transfection ,Metastasis ,Small hairpin RNA ,Lipocalin-2 ,Cell Movement ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Gene silencing ,Humans ,Gene Silencing ,RNA, Messenger ,Cytoskeleton ,Cervical cancer ,Tissue microarray ,business.industry ,Aldo-Keto Reductase Family 1 Member C3 ,Obstetrics and Gynecology ,Cancer ,Cell migration ,medicine.disease ,Prognosis ,Lipocalins ,HEK293 Cells ,Oncology ,Cancer research ,Disease Progression ,Hydroxyprostaglandin Dehydrogenases ,Matrix Metalloproteinase 2 ,Female ,Neoplasm Recurrence, Local ,business ,Acute-Phase Proteins ,HeLa Cells - Abstract
Objective Over-expression of the aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated in many human cancers. Lipocalin 2 (LCN2) is reported to inhibit cervical cancer metastasis but little is known regarding its relationship with AKR1C3 in the development and progression of uterine cervical cancer. This study aimed to investigate the involvement of AKR1C3 and its relationship with LCN2 in cervical cancer. Methods The roles of AKR1C3 and LCN2 were investigated using the lentivirus shRNA system in SiHa and Caski cervical cancer cells. LCN2 and matrix metalloproteinase-2 (MMP-2) promoters were constructed to demonstrate transcriptional regulation by shAKR1C3 and shLCN2, respectively. The influences of metastatic phenotypes were analyzed by wound healing, Boyden chamber, and immunofluorescence assays. The activity of MMP-2 was determined by zymography assay. The impacts of AKR1C3 and LCN2 on patient prognosis were evaluated using tissue microarrays by Cox regression and Kaplan–Meier models. Results Silencing of the AKR1C3 gene increased the expression of LCN2 and decreased the migratory and invasive abilities and changed the cytoskeleton of cervical cancer cells. When AKR1C3 was over-expressed, it decreased LCN2 promoter activity and LCN2 expression and increased cell migration. The mRNA level and enzyme activity of MMP-2 increased in silenced LCN2 cells. Positive AKR1C3 and negative LCN2 were correlated with higher recurrence and poorer survival of cervical cancer patients. Conclusions Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. Both AKR1C3 and LCN2 serve as molecular targets for cancer therapy to improve the clinical outcome of cervical cancer patients.
- Published
- 2013
36. HER2 amplification and overexpression are significantly correlated in mucinous epithelial ovarian cancer
- Author
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Wan-Ru Chao, Chi-Kuan Chen, Gwo-Tarng Sheu, Chih-Ping Han, Ming-Yung Lee, Wea-Long Lin, Jau-Chen Lin, and Chiew-Loon Koo
- Subjects
Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Gene Dosage ,Biology ,Pathology and Forensic Medicine ,Trastuzumab ,medicine ,Humans ,skin and connective tissue diseases ,neoplasms ,Gene ,In Situ Hybridization, Fluorescence ,Ovarian Neoplasms ,Tissue microarray ,medicine.diagnostic_test ,Hybridization probe ,Gene Expression Profiling ,Gene Amplification ,Cancer ,Genes, erbB-2 ,medicine.disease ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,Tissue Array Analysis ,Cancer research ,biology.protein ,Female ,Antibody ,medicine.drug ,Fluorescence in situ hybridization ,Chromosomes, Human, Pair 17 - Abstract
HER2 gene amplification and protein over-expression are important factors in predicting clinical sensitivity to anti-HER2 therapies in breast, gastric or gastroesophageal junction cancer patients. The aim of this study was to evaluate the correlation between HER2 gene copy numbers and HER2 protein expressions in mucinous epithelial ovarian cancer (EOC). Of the 49 tissue microarray samples of mucinous EOC, we applied 2010 ToGA trial (Trastuzumab for Gastric Cancer) surgical specimen scoring criteria to analyze the HER2 protein expression by an immunohistochemistry (IHC) test with Dako (Carpenteria, CA), c-erb-B2 antibody, and the HER2 gene amplification by the fluorescence in situ hybridization (FISH) test with Abbott/Vysis PathVysion HER2 DNA Probe Kit (Abbott Molecular Inc., Des Plaines, IA). We achieved a high overall concordance of 97.56% between nonequivocal HER2 results by IHC and FISH tests. In addition, HER2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal and positive IHC result categories (P
- Published
- 2013
37. Mutational analysis of human papillomavirus type 11 E5a oncoprotein
- Author
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Chih-Ping Han, Shiou Lan Chen, Tung-Han Tsai, and Y. P. Tsao
- Subjects
Molecular Sequence Data ,Immunology ,Mutant ,Biology ,Transfection ,medicine.disease_cause ,Microbiology ,Mice ,Structure-Activity Relationship ,Virology ,medicine ,Animals ,Structure–activity relationship ,Amino Acid Sequence ,Papillomaviridae ,Peptide sequence ,Adenosine Triphosphatases ,chemistry.chemical_classification ,Mutation ,COS cells ,Base Sequence ,3T3 Cells ,Oncogene Proteins, Viral ,Molecular biology ,Amino acid ,Transformation (genetics) ,Cell Transformation, Neoplastic ,chemistry ,Biochemistry ,Insect Science ,Vacuoles ,Research Article - Abstract
In this study, we investigated the structural basis of human papillomavirus type 11 (HPV-11) E5a transforming activity at the amino acid level. The effects of insertion, deletion , and substitution mutations on teh E5a transforming activity were determined by the assay of anchorage-independent growth. In the conserved Cys-X-Cys structure, substitution of Ser for Cys-73 resulted in indistinguishable transforming activity, whereas substitution of Ser for Cys-75 or Ser for both Cys-73 and Cys-75 retained 50 and 42% transformation, respectively. This suggests that Cys at position 75 may be important for transformation. Charge and structural changes at teh COOH termini of several mutants impaired transformation significantly, but those at the middle region did so only mildly. In addition, the 16,000-molecular-weight pore-forming protein (16K protein) is known to associate with BPV-1, HPV-6, and HPV-16 E5 proteins. In this study, we investigated the correlation between E5a-16K binding affinity and the transforming activity of E5a by the use of 11 E5a mutants. Results show that E5a and these 11 E5a mutants could bind to the 16K protein when these proteins were coexpressed in COS cells, suggesting that simple binding of the 16K protein by E5a may not be sufficient for cell transformation.
- Published
- 1996
38. Coincidental expression of E5a and c-jun in human papillomavirus type 6/11-infected condylomata
- Author
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Show Li Chen, Chih-Ping Han, Tzu-Bou Hsieh, Yung-Fu Yang, and Yeou-Ping Tsao
- Subjects
Keratinocytes ,Male ,Transcription, Genetic ,Proto-Oncogene Proteins c-jun ,In situ hybridization ,Biology ,3T3 cells ,Mice ,Genes, jun ,Transcription (biology) ,Virology ,Gene expression ,medicine ,Animals ,Humans ,RNA, Messenger ,Papillomaviridae ,Gene ,Cells, Cultured ,In Situ Hybridization ,Retrospective Studies ,Skin ,Messenger RNA ,c-jun ,virus diseases ,RNA ,3T3 Cells ,Oncogene Proteins, Viral ,medicine.anatomical_structure ,Condylomata Acuminata ,Female - Abstract
Previously, we have shown that E5a can induce ex pression of the c-jun gene in human papillomavirus (HPV)-11 E5a transformed NIH 3T3 cells and human epidermal keratinocytes. In this study, we investigated the relationship between expression of the E5a gene and c-jun in pathologically confirmed condylomata specimens using mRNA hybridization in situ. The c-jun RNA concentration was significantly higher in condylomata specimens with E5a mRNA expression than in specimens without E5a mRNA expression, or in normal cervical specimens. The cells with c-jun expression were located predominantly in the basal and parabasal cell layers. These layers were also the primary location of E5a-expressing cells. This is the first demonstration of a strong correlation (74%) between expression of the E5a and c-jun genes in condylomata specimens. This correlation might reflect regulation by HPV-11 E5a of c-jun gene expression in condyloma.
- Published
- 1996
39. Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: Frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions
- Author
-
Kong-Bung Choo, Lo-Chun Au, Winston T.K. Cheng, Chih-Ping Han, and Chuan-Mu Chen
- Subjects
Genetics ,Sequence analysis ,Chromosomal fragile site ,Cancer ,Locus (genetics) ,Biology ,medicine.disease ,biology.organism_classification ,Virology ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,medicine ,Papillomaviridae ,Virus Integration ,Gene ,DNA - Abstract
To discern the structural features of cellular loci that are disrupted by type 16 human papillomavirus (HPV-16) integration in cervical cancer, a polymerase chain reaction (PCR)-based strategy was employed for direct amplification and sequence analysis of four such cellular loci in cancer biopsy samples. One of the HPV-16-disrupted loci was found to be the microtubule-associated protein (MAP-2) gene and the other three loci were uncharacterized and were designated PID-1 to -3 (for papillomavirus integration-disrupted). The junctional sequences of the viral integration sites in the four loci analyzed are bracketed by long tracts of homogeneous purine or pyrimidine or alternating purine-pyrimidine which are known to destabilize the B-form conformation of the DNA structure. Using a panel of human/hamster hybrid cell DNAs and PCR analysis, the four loci were assigned to chromosomes 2 (MAP-2), 9 (PID-1), 1 (PID-2) and 8 (PID-3), respectively. These chromosomes carry numerous other previously determined viral integration and chromosomal fragile sites and the myc oncogenes. The PID-1 locus was further found in Southern analysis to be rearranged and amplified in another cervical cancer biopsy and a cervical carcinoma cell line (CaSki). On Northern analysis, the PID-1 and -3 probes detected a 3.0- and a 3.6-kb transcript, respectively, in normal cervical cells and in cervical cancer cell lines. The findings suggest that HPV-16 genome integrates frequently into topologically destabilized and transcriptionally active chromosomal sites. It remains to be elucidated whether the MAP-2 and the PID loci contribute to the pathogenesis of cervical cancer.
- Published
- 1996
40. Jun-B oncogene aberrations in cervical cancer cell lines
- Author
-
Lo-Chun Au, Kong-Bung Choo, Chuan-Mu Chen, Chih-Ping Han, and Chiu-Jung Huang
- Subjects
Cancer Research ,DNA, Complementary ,Uterine Cervical Neoplasms ,Chromosomal translocation ,Locus (genetics) ,Transfection ,Translocation, Genetic ,HeLa ,Chromosome 15 ,Genes, jun ,Chromosome 19 ,Tumor Cells, Cultured ,Humans ,Papillomaviridae ,Gene ,Alleles ,Regulation of gene expression ,biology ,Oncogene ,DNA, Neoplasm ,biology.organism_classification ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Oncology ,Female ,Polymorphism, Restriction Fragment Length ,HeLa Cells - Abstract
We describe here structural and expression analysis of the jun-B oncogene in two cervical cancer cell lines. In the CC7T-a cell line, results from both Southern analysis and cDNA cloning studies revealed the existence of two structurally altered jun-B alleles besides the normal gene. One of the altered alleles was due to a type 16 human papillomavirus (HPV-16) integration event, whereas the other allele was a consequence of a chromosomal translocation involving chromosome 19 (jun-B) and an EST182 locus residing in chromosome 15. In the HeLa cell line, which contains integrated HPV-18, an apparent structural aberration, a 3-fold amplification and a 3-fold overexpression of the jun-B gene were observed. Our observations suggest that deregulation of the jun-B gene expression may have contributed to the transformation process in these two cervical cancer cell lines.
- Published
- 1995
41. Genital human papillomavirus infections in Taiwan
- Author
-
Show-Li Chen, Yung-Fu Yang, C.S. Yin, Y.P. Tsao, Chih-Ping Han, and K.Y. Yang
- Subjects
Adult ,Male ,Sexually transmitted disease ,medicine.medical_specialty ,Population ,Taiwan ,Uterine Cervical Neoplasms ,Uterine Cervical Diseases ,Risk Factors ,Cytology ,medicine ,Humans ,Papillomaviridae ,education ,Cervix ,Vaginal Smears ,Cervical cancer ,Gynecology ,education.field_of_study ,biology ,business.industry ,Papillomavirus Infections ,HPV infection ,Nucleic Acid Hybridization ,virus diseases ,Obstetrics and Gynecology ,General Medicine ,Middle Aged ,Condyloma Acuminatum ,medicine.disease ,biology.organism_classification ,female genital diseases and pregnancy complications ,Blotting, Southern ,medicine.anatomical_structure ,Condylomata Acuminata ,DNA, Viral ,Female ,business - Abstract
OBJECTIVES: Identification and typing of HPV infections in genital condyloma and normal cytological cervix. METHODS: Cervical cells from 289 Pap cases with normal cytological findings were examined for HPV infection by slot blot hybridization. Fifteen condyloma biopsy specimens were studied by Southern blot hybridization. RESULTS: Thirty-six cases (12.5%) with normal cervical cytology were HP V positive. The predominant HPV type in women with normal cytology is HPV-16. Risk factors for HPV infection in women with normal cytology depend on age and history of pregnancies. Twelve cases (80%) of condyloma contained HP V-6 or-11 sequences. The predominant HPV type in genital condyloma is HPV-11. CONCLUSIONS: HPV detection in population-based screening programs for cervical neoplasia can be an important tool in identifying women who are at risk of developing dysplasia and cervical cancer.
- Published
- 1994
42. Source of anti-cytokeratin CAM 5.2 reagent
- Author
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Wea-Lung Lin, Chih-Ping Han, Fong-Lin Chen, and Ming-Yung Lee
- Subjects
Neoplasms, Multiple Primary ,Cytokeratin ,Esophageal Neoplasms ,Chemistry ,Reagent ,Humans ,Surgery ,Female ,Neuroectodermal Tumors, Primitive, Peripheral ,Sarcoma, Ewing ,Anatomy ,Molecular biology ,Pathology and Forensic Medicine - Published
- 2011
43. Assessing the impact of polysomy-17 on HER2 status and the correlations of HER2 status with prognostic variables (ER, PR, p53, Ki-67) in epithelial ovarian cancer: a tissue microarray study using immunohistochemistry and fluorescent in situ hybridization
- Author
-
Alexandra Ruan, Ming-Chih Chou, Fong-Lin Chen, Chih-Kuang Lin, Jang-Fang Kuo, Hung Chiang, Wea-Lung Lin, Chih-Ping Han, Yeu-Sheng Tyan, and Ming-Yung Lee
- Subjects
Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Estrogen receptor ,Gene Expression ,In situ hybridization ,Biology ,Pathology and Forensic Medicine ,Progesterone receptor ,medicine ,Humans ,skin and connective tissue diseases ,neoplasms ,In Situ Hybridization, Fluorescence ,Ovarian Neoplasms ,Polysomy ,Tissue microarray ,medicine.diagnostic_test ,Obstetrics and Gynecology ,medicine.disease ,Aneuploidy ,Microarray Analysis ,Prognosis ,Immunohistochemistry ,Ki-67 Antigen ,Receptors, Estrogen ,Ki-67 ,biology.protein ,Female ,Tumor Suppressor Protein p53 ,Receptors, Progesterone ,Fluorescence in situ hybridization ,Chromosomes, Human, Pair 17 - Abstract
Although HER2 overexpression and Her2 amplification have been noted in breast and a variety of human cancers, we report here for the first time the impact of polysomy-17 on HER2 status and the correlations between HER2 status and other prognostic factors in patients with epithelial ovarian cancers (EOC).We analyzed HER2, estrogen receptor (ER), progesterone receptor (PR), p53, and Ki-67 protein overexpressions by immunohistochemistry (IHC) and determined Her2 gene amplification by fluorescence in situ hybridization (FISH) in 27 tissue microarray samples from EOC patients.We achieved 100% positive concordance (3/3) and 100% negative concordance (19/19) between HER2 testing by IHC and FISH. Both the total Her2 gene copies and FISH scores increased significantly in a stepwise order through the negative, equivocal, and positive HER2 IHC result categories in all 27 cases (P=0.001, P=0.001), and still increased significantly in 18 nonpolysomy-17 cases (P=0.007 and 0.013) after the exclusion of 9 polysomy-17 cases. HER2 protein expression is inversely correlated with both ER (P=0.002) and PR expressions (P=0.046). Her2 gene amplification is inversely correlated with ER expression (P=0.007) but not with PR expression (P=0.106).This study showed extremely high positive and negative concordances between Her2 FISH and HER2 IHC assays. Polysomy-17 is insufficient for causing a significant impact on the relationship between HER2 testing by IHC and FISH in EOC. ER and PR expressions were inversely correlated with HER2 protein expression. In addition, ER but not PR expression is inversely correlated with Her2 gene amplification.
- Published
- 2011
44. Overexpression of c-KIT (CD117) occurs infrequently in squamous cell carcinoma of the uterine cervix
- Author
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Chih-Ping, Han, Wea-Lung, Lin, Wea-Long, Lin, Po-Hui, Wang, Shun-Fa, Yang, James S, Lewis, Chi-Kuan, Chen, Alexandra, Ruan, Jang-Fang, Kuo, Ming-Yung, Lee, and Hung, Chiang
- Subjects
Gene Expression Regulation, Neoplastic ,Proto-Oncogene Proteins c-kit ,Biomarkers, Tumor ,Carcinoma, Squamous Cell ,Humans ,Uterine Cervical Neoplasms ,Female ,Microarray Analysis - Published
- 2011
45. CAM 5.2 shows specific reactivity for cytokeratin 8, but less strict reactivity for cytokeratin 7 and no reactivity for cytokeratin 18: in response to 'Fujikawa T, Tanaka A, Abe T et al. 'Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: report of a case'. Surg today 2011;41(4):579-84.'
- Author
-
Chi-Kuan Chen, Wan-Ru Chao, Chiew-Loon Koo, and Chih-Ping Han
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Common bile duct ,business.industry ,Carcinoma ,Common Bile Duct Neoplasms ,Thrombosis ,General Medicine ,Cytokeratin ,medicine.anatomical_structure ,Surgical oncology ,Keratin 8 ,Medicine ,Humans ,Surgery ,Reactivity (chemistry) ,Undifferentiated carcinoma ,business - Published
- 2011
46. Significant relation of tissue inhibitor of matrix metalloproteinase-2 and its combination with matrix metalloproteinase-2 to survival of patients with cancer of uterine cervix
- Author
-
Chih Ping Han, Hsiu Ting Tsai, Po Hui Wang, Shun-Fa Yang, Yang Tse Shih, Jiunn-Liang Ko, Shiuan Chih Chen, Yi Torng Tee, and Long Yau Lin
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Uterine Cervical Neoplasms ,Kaplan-Meier Estimate ,Matrix (biology) ,Matrix metalloproteinase ,Internal medicine ,medicine ,Overall survival ,Humans ,RNA, Neoplasm ,Adverse effect ,Cervical cancer ,Tissue Inhibitor of Metalloproteinase-2 ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Obstetrics and Gynecology ,Cancer ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Tissue Array Analysis ,Matrix Metalloproteinase 2 ,Female ,DNA microarray ,business - Abstract
Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) has high affinity for matrix metalloproteinase-2 (MMP-2). Few studies simultaneously investigate their implication in prognosis of patients with cervical cancer. We used reverse transcription-polymerase chain reaction and immunohistochemical method for cervical tissues and microarrays to investigate the association among TIMP-2, MMP-2, clinicopathological parameters, and prognosis of patients with cancer. Our results showed that cancer tissues exhibited less TIMP-2 expression and patients with pelvic lymph node metastasis had less TIMP-2 expression. Positive TIMP-2 constellated with negative MMP-2 indicated lower recurrence probability and better overall survival. The protective effect of TIMP-2 expression may overcome the adverse effect of MMP-2 expression in terms of disease-free interval and overall survival while neither TIMP-2 nor MMP-2 alone can be used to predict outcome. We suggest that following patients other than those with positive TIMP-2 and negative MMP-2 expression more closely and intensely may improve their prognosis.
- Published
- 2011
47. Identification and typing of human papillomavirus in cervical cancers in taiwan
- Author
-
Chih-Ping Han, B D Jeng-Woei Lee, Chang-Sheng Yin, Yeou-Ping Tsao M.D., and Show-Li Chen
- Subjects
Cervical cancer ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Epithelioma ,business.industry ,virus diseases ,Cancer ,medicine.disease ,female genital diseases and pregnancy complications ,law.invention ,medicine.anatomical_structure ,law ,Internal medicine ,medicine ,Carcinoma ,Typing ,Restriction fragment length polymorphism ,business ,Cervix ,Polymerase chain reaction - Abstract
Background. Although human papillomaviruses (HPV) are associated with cervical cancer, it has yet to be determined if specific HPV types have clinical or prognostic significance. Methods. Identification and typing of HPV were done by polymerase chain reaction (PCR) and restriction fragment length polymorphism. Results. Of the 43 cases of cervical cancer, 31 (72%) were HPV positive. The results of HPV typing in 40 cases of squamous cell carcinoma of the cervix revealed the presence of HPV-16 in 20 cases (50%), HPV-18 in 2 cases, HPV-11 in 1 case, HPV-33 in 1 case, HPV-52 in 1 case, HPV-58 in 1 case, and unidentified HPV types in 5 cases. Neither HPV-31 nor HPV-42 were present in our study. One case of squamous cell carcinoma had HPV-11 integration. Chi-square analysis revealed significant correlation between HPV genotypes and squamous cell patterns, no significant correlation between HPV genotypes and clinical stages, and cell differentiation of squamous cell carcinoma of cervix. Conclusions. These findings may contribute to understanding the role of HPV in cancer and the value of typing as a prognostic indicator.
- Published
- 1993
48. Construction of site-specific mutants of E5A protein of HPV-11 using the polymerase chain reaction and a single mutant primer
- Author
-
Yeou-Ping Tsao, Show-Li Chen, and Chih-Ping Han
- Subjects
Base Sequence ,Sequence Homology, Amino Acid ,Inverse polymerase chain reaction ,Molecular Sequence Data ,Mutant ,Mutagenesis (molecular biology technique) ,Oncogene Proteins, Viral ,Biology ,Polymerase Chain Reaction ,Molecular biology ,law.invention ,chemistry.chemical_compound ,chemistry ,law ,Sequence Homology, Nucleic Acid ,Virology ,Multiplex polymerase chain reaction ,Mutagenesis, Site-Directed ,Amino Acid Sequence ,Primer (molecular biology) ,Site-directed mutagenesis ,Papillomaviridae ,Polymerase chain reaction ,DNA ,Repetitive Sequences, Nucleic Acid - Abstract
The method of Perrin and Gilliland (1990) was modified to create site-specific mutants. The polymerase chain reaction and a single mutant primer are needed to carry out site-specific mutagenesis. Using this method, removal of the excess primers and nucleotides from the initial amplification is not necessary. This method provides a simpler way to generate site-specific mutants.
- Published
- 1993
49. Anticytokeratin (CAM5.2) Reagent Identifies Cytokeratins 7 and 8, Not Cytokeratin 18
- Author
-
Kuang-Leei Chang, Chih-Ping Han, and Wan-Ru Chao
- Subjects
Pulmonary and Respiratory Medicine ,Cytokeratin ,Pathology ,medicine.medical_specialty ,business.industry ,Reagent ,Medicine ,Immunohistochemistry ,Pleural Neoplasm ,Cardiology and Cardiovascular Medicine ,Critical Care and Intensive Care Medicine ,business - Published
- 2014
50. HER2 gene amplification in primary mucinous ovarian cancer: a potential therapeutic target
- Author
-
Chih-Ping, Han, Jeng-Dong, Hsu, Chung-Chin, Yao, Ming-Yung, Lee, Alexandra, Ruan, Yeu-Sheng, Tyan, Shun-Fa, Yang, and Hung, Chiang
- Subjects
Ovarian Neoplasms ,Receptor, ErbB-2 ,Gene Amplification ,Humans ,Female ,Adenocarcinoma, Mucinous - Published
- 2010
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