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PurposeIn this study, we investigated the frequencies of mutations in DNA damage repair genes including BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian high-grade serous carcinoma, alongside those of germline and somatic BRCA mutations, with the aim of improving the identification of patients suitable for treatment with poly(ADP-ribose) polymerase inhibitors.Materials and MethodsTissue samples from 77 Korean patients with ovarian high-grade serous carcinoma were subjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repair genes and TP53 gene and their relationships with patient survival were examined. Additionally, we analyzed BRCA germline variants in blood samples from 47 of the patients for comparison.ResultsBRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77 patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified. At least one mutation in a DNA damage repair gene was detected in 40.3% of patients (31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%), and four patients had only somatic mutations without germline mutations (8.5%, 4/47). Patients with DNA damage repair gene alterations with or without TP53mutation, exhibited better disease-free survival than those with TP53 mutation alone.ConclusionDNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma, with somatic BRCA mutations in the absence of germline mutation in 8.5%. Somatic variant examination, along with germline testing of DNA damage repair genes, has potential to detect additional candidates for PARP inhibitor treatment.

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.

Fibulin-5 is an extracellular matrix (ECM) glycoprotein which has a role in the organisation and stabilisation of ECM structures and regulating cell proliferation and tumourigenesis. Here, the expression of fibulin-5 and its functional effects on the migration and invasion of ovarian cancer cells were assessed.Expression of fibulin-5 was detected in 44 ovarian tumour tissues by qRT-PCR, Western blotting and immunohistochemistry. We performed cell migration and invasion assays, and cell cycle analysis in fibulin-5 transfected SKOV3 (SKOV3-FBLN5) cells and the parental SKOV3 cells. We further examined the expression of three tissue inhibitors of metalloproteinases (TIMPs) and seven matrix metalloproteinases (MMPs) by RT-PCR.mRNA and protein expression of fibulin-5 were down-regulated (0.05-fold and 0.1-fold) in ovarian carcinomas compared with control tissues (p0.01 and p=0.022). In wound-healing and invasion assays, significantly fewer SKOV3-FBLN5 cells than SKOV3 control cells migrated and invaded (39.1%, p=0.046 and 70%, p=0.03, respectively), which was reversed by siRNA-treatment. Overexpression of fibulin-5 induced G2/M arrest and increased cyclin B1, CDC2 and CDC25C. Expression of TIMP-2 (0.56-fold), MMP-3 (0.43-fold) and MMP-13 (0.18-fold) was lower and MMP-9 expression (2.20-fold) was higher in SKOV3-FBLN5 cells than in control cells.Fibulin-5 is significantly down-regulated in ovarian carcinoma and acts as a tumour suppressor by inhibiting the migration and invasion of ovarian cancer cells.

Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P

MicroRNA-145 (miR-145) expression is downregulated in several human cancers, but its clinical and functional relevance to ovarian carcinoma has not yet been elucidated. This study addressed the hypothesis that miR-145 serves as a prognostic biomarker and a tumor suppressor that regulates the expression of high-mobility group A2 (HMGA2) oncoprotein in ovarian cancer. Here, we found that low miR-145 expression and HMGA2 overexpression determined by qRT-PCR and immunohistochemistry significantly correlated with advanced stage, lymph node involvement, and distant metastasis in 74 ovarian carcinomas. Low miR-145 expression significantly correlated with tumor recurrence and worse overall survival (HR=8.62, P = 0.039). Transfection of pre-miR-145 resulted in reduced cell growth and migration, and increased apoptosis of ovarian cancer cells by TUNEL, colony forming, and cell migration assays. MiR-145 was found to directly target HMGA2 by luciferase assay and Western blotting. Our findings suggest that miR-145 functions as a tumor suppressor in ovarian cancer and directly targets HMGA2 oncoprotein. Low miR-145 and high HMGA2 expressions are potential biomarkers of poor prognosis of ovarian carcinoma and miR-145 is the more powerful predictor of patient outcome.

Calcifying aponeurotic fibroma is a rare, benign fibroblastic tumor that typically occurs in the palms of the hands and soles of the feet in children and adolescents. We report an unusual case of a calcifying aponeurotic fibroma with diffuse intra-articular involvement of the carpal joints in a 59-year-old female. Radiographs and computed tomography scans revealed a large lobulated soft tissue mass with multiple stippled calcifications around the carpal joints and numerous erosions of the second to fifth carpometacarpal and intercarpal joints. Magnetic resonance imaging showed diffuse multinodular synovial proliferation with inhomogeneous hypo- to isointense signal intensity on T1-weighted images, inhomogeneous hypointense to hyperintense signal intensity on T2-weighted images, and inhomogeneous intense enhancement on fat-suppressed contrast-enhanced T1-weighted images. Radiologic diagnosis included gout, calcium pyrophosphate dihydrate deposition disease, and tenosynovial giant cell tumor. Surgical excision was performed, and the mass was diagnosed on pathologic examination as a calcifying aponeurotic fibroma. There has been no reported case of a calcifying aponeurotic fibroma with diffuse intra-articular involvement of the carpal joints in the literature.

The principal objective of this study was to comprehensively assess the clinicopathologic and prognostic impacts of the expression of various cell cycle regulatory proteins in patients with ovarian epithelial tumors. The tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissues of 205 ovarian epithelial tumors. We investigated 55 benign (20 serous cystadenomas, 17 mucinous cystadenomas, and 18 endometriotic cysts), 72 borderline (26 serous borderline tumors and 46 mucinous borderline tumors), and 78 malignant tumors (45 serous carcinomas, 10 mucinous adenocarcinomas, 15 endometrioid adenocarcinomas, and 8 clear cell carcinomas). Immunohistochemical staining was performed using antibodies to p16(Ink4a), p53, p21(Waf1/Cip1), p27(Kip1), Cyclin D1, Cyclin E, Cyclin A, Cyclin B1, and Cyclin-dependent Kinase2. We noted significantly different levels of p53 and Cyclin B1 expressions between malignant and borderline tumors and between borderline and benign tumors excepting the mucinous type. The p21(Waf1/Cip1) and Cyclin A were significantly overexpressed in malignant tumors compared with borderline tumors. Cyclin A, Cyclin E, and p16(Ink4a) were more pronounced proteins, showing differential expression patterns among the histologic types of ovarian carcinomas. We determined that the overexpression of p16(Ink4a) (P=0.031), Cyclin E (P=0.009), and Cyclin-dependent Kinase2 (P=0.004) were significantly associated with higher tumor grades. Overexpression of p16(Ink4a) was correlated with both lymph node metastasis (P=0.030) and distant metastasis (P=0.034). Overexpression of Cyclin E was associated with advanced stage (P=0.004). Higher tumor grade (P=0.008), advanced stage (P=0.001), mucinous histologic type (P=0.012), low expression levels of p16(Ink4a) (P=0.032), and overexpression of p53 (P=0.032) were associated with poor overall survival on multivariate analysis in patients with ovarian cancer. In serous carcinomas, old age (P=0.005), distant metastasis (P=0.020), low expression of p16(Ink4a) (P=0.047), and overexpression of cytoplasmic p27(Kip1) (P=0.007) and Cyclin A (P=0.031) were all independent predictors of worse overall survival. Our data indicate that the overexpression of p16 and Cyclin E are valuable factors predicting disease progression and metastatic potential. Low p16(Ink4a) expression, overexpression of p53, cytoplasmic p27(Kip1), and Cyclin A are predictive markers for shorter overall survival in ovarian carcinomas.

Endometriosis is a common gynaecologic disease involving the ectopic growth of endometrial glands and stroma outside the uterus. The most commonly affected organs are the ovaries and other pelvic s...

Sox10 is a transcription factor regulating the development of several cell lineages and is involved in tumor development. However, the clinicopathological relevance of Sox10 expression in ovarian cancer has not been examined. We assessed expression of Sox10 in ovarian epithelial tumors by immunohistochemistry and assessed its prognostic value by analyzing the correlation between its expression and clinicopathological factors. We used tissue microarrays including 244 ovarian epithelial tumors. Sox10 staining was found in the cytoplasm or nucleus of tumor cells. Malignant serous, mucinous, and endometrioid tumors were significantly more likely to express Sox10 than benign and borderline tumors. Expression patterns in adenocarcinomas were different for histologic subtypes: nuclear Sox10 staining was common in clear-cell adenocarcinomas and serous adenocarcinomas, whereas all cases of mucinous and endometrioid tumors were negative for nuclear staining. Nuclear Sox10 staining was also associated with chemoresistance and shorter overall survival in ovarian adenocarcinomas, notably in high-grade serous adenocarcinoma. Sox10 is expressed in many ovarian carcinomas, suggesting that it might be involved in oncogenesis of ovarian carcinoma. Expression pattern of Sox10 differs between histological subtypes. Nuclear Sox10 expression is an independent indicator of poor prognosis in ovarian adenocarcinomas, notably in high-grade serous adenocarcinomas.

Chondromyxoid fibroma is a rare benign bone tumor, which represents less than 1% of primary bone tumors. However, chondromyxoid fibroma developing in the soft tissue is extremely rare. We report the sonographic findings in a case of soft tissue chondromyxoid fibroma in the foot confirmed pathologically.

Fascin1 (FSCN1) involved in cell motility and filopodia assembly plays important roles in biological processes such as cancer invasion and metastasis of multiple epithelial tumors. High-grade serous ovarian carcinoma (HGSOC) is aggressive and metastatic by acquiring an invasive phenotype and this step requires remodeling of the actin cytoskeleton. Thus, the present study aimed to investigate the expression of fascin1 in HGSOC tissues as well as its clinical significance such as prognostic predictors and its utility of therapeutic target. Fascin1 and β-catenin were evaluated using immunohistochemistry on a tissue microarray of 79 HGSOC. Small interfering RNA (siRNA) approach was used to knock down fascin1 expression in ovarian cancer cell lines to determine whether fascin1 contributes to tumor cell proliferation, migration and invasion. Fascin1 expression levels were determined by western blot analysis after siRNA transfection using two human ovarian cancer cell lines (SKOV3 and OVCAR3). Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P

Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is difficult. We have compared colon crypts, which are putatively clonal and contain ~2000 cells each, to determine how much somatic genetic variation occurs in vivo (without ex vivo cell culturing). Using high-density SNP microarrays, we find that chromosome deletions, duplications, and gene conversions were significantly more frequent in colons from the older individuals. These changes affected lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a single mutant stem cell to reach niche dominance over neighboring stem cells, none of the deletions appear likely to confer a selective advantage. Mutations can become fixed randomly during stem cell evolution through neutral drift in normal human crypts. The fact that chromosomal changes are detected in individual crypts with increasing age suggests that either such changes accumulate with age or single stem cell dominance increases with age, and the former is more likely. This progressive genome-wide divergence of human somatic cells with age has implications for aging and disease in multicellular organisms.

Notch signalling plays diverse roles in malignant tumours as well as in normal tissue development. In this study we investigated the expression of Notch signalling pathway genes and their clinicopathological significance in gastric carcinomas.Notch1, Notch3, Jagged1, Jagged2 and Hes1 expression were analysed by quantitative real-time polymerase chain reaction (qRT-PCR) (n = 81) and immunohistochemistry (n = 103) in gastric carcinomas. MUC2 and MUC5AC expression were also assessed, using immunohistochemistry only. With qRT-PCR, Notch1, Notch3, Jagged1 and Jagged2 expression were increased significantly in tumour compared to normal tissue (P 0.001, P = 0.002, P = 0.008 and P 0.001, respectively). Overexpression of Notch3 and Jagged2 was associated with intestinal-type carcinomas (P = 0.024) and better histological differentiation (P = 0.047), respectively. Immunohistochemistry showed a reverse correlation between MUC2 and Notch3 or Jagged1 (P = 0.033 and P = 0.005, respectively) and between MUC5AC and Jagged1 or Hes1 (P = 0.004 and P = 0.002, respectively). Notch3 and Jagged2 gene overexpression related to a favourable outcome on univariate (P = 0.046 and P = 0.042, respectively) and multivariate (P = 0.045, Notch3) analysis.The expression of Notch3 and Jagged2 is associated not only with gastric cancer development but also with the intestinal/glandular differentiation of gastric carcinoma cells, suggesting a role as a possible favourable prognostic indicator.

The pathological and clinical significance of aberrant miRNA expression in ovarian tumours has yet to be adequately documented. The aim of this study was to assess the differences in miRNA expression of human ovarian tumours according to histological subtype, and to determine whether miRNAs are potential diagnostic and prognostic markers in ovarian cancers.The miRNA expression profiles of 103 human ovarian tumours were evaluated. Via a bead-based miRNA microarray, five aberrant miRNAs were selected which were expressed differentially in malignant serous tumours from borderline and benign ovarian tumours, including miRNA (miR)-519a, miR-18b (up-regulation) and miR-153, miR-511 and miR-485-5p (down-regulation). We conducted quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in order to confirm that these miRNAs are differentially expressed in different histological subtypes of ovarian tumours, and compared the expression profiles of these miRNAs between different clinical subsets. The expression of these miRNAs was correlated with clinicopathological parameters. miR-519a, miR-153 and miR-485-5p were differentially expressed in four major histotypes of ovarian cancers (P0.05), which suggests that they might be of potential importance as diagnostic biomarkers. Down-regulation of miR-153 and miR-485-5p was correlated significantly with FIGO grade 3 (P0.05). Down-regulation of miR-153 and up-regulation of miR-519a were correlated significantly with advanced clinical stage (P0.05). The results of Kaplan-Meier survival analysis indicated that the higher expression of miR-519a in late stage serous carcinoma was associated significantly with poor progression-free survival (P = 0.0058).A significant correlation was detected between the deregulation of specific types of miRNAs, such as miR-519a, miR-153 and miR-485-5p, and clinical variables as well as histological subtypes in ovarian cancers. Hence, these miRNAs may perform functions as diagnostic or prognostic biomarkers.

Degenerative disorders of the intervertebral discs (IVDs) are generally characterized by enhanced matrix degradation, angiogenesis, innervation, and increased expression of catabolic cytokines. In this study, we investigated the effects of inflammatory cytokines, IL-1β, and TNF-α, on the expression of an angiogenic factor, vascular endothelial growth factor (VEGF), and neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in human IVD degeneration. IL-1β and TNF-α stimulated the gene expression of VEGF, NGF, and BDNF in nucleus pulposus (NP) cells isolated from patient tissues. Immunohistochemical results demonstrated a positive correlation between IL-1β and VEGF/NGF/BDNF expression in human IVD tissues. RNA expression analysis of patient tissues also identified positive correlations between VEGF and platelet endothelial cell adhesion molecule-1 (PECAM-1) and between NGF/BDNF and protein gene product 9.5 (PGP9.5). Our findings suggest that IL-1β is generated during IVD degeneration, which stimulates the expression of VEGF, NGF, and BDNF, resulting in angiogenesis and innervation.

Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP. Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer.These types of TS polymorphism were investigated in 318 gastric cancer patients and 280 controls. A variable number of tandem repeats (VNTR; 2R or 3R) in the thymidylate synthase enhancer region (TSER), a G/C single nucleotide polymorphism within the second repeat sequence of 3R (3G or 3C), and a 6 bp insertion/deletion polymorphism (6 bp or 0 bp) in the TS 3'-untranslated region (3'-UTR) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients were sub-grouped by the Lauren classification.The TSER 2R/2R genotype had a high odds ratio in gastric cancer and for the intestinal type, but was not statistically significant (adjusted odds ratio, AOR=2.31, 95% confidence interval, CI=0.94-5.65; and AOR=2.53, 95% CI=0.98-6.54, respectively). Among the combined genotypes of TSER VNTR-3'-UTR 6 bp ins/del, 2R2R-6 bp/6 bp having 4 risk alleles conferred a significantly high risk of gastric cancer, particularly of the intestinal type (AOR=8.70, 95% CI=1.09-68.93; and AOR=10.86, 95% CI=1.32-89.09, respectively).Our results indicate that the 2R/2R-6 bp/6 bp combined genotype may be related to high gastric cancer susceptibility.

Angiogenesis plays an important role in the growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the present case-control study to determine whether there is an association between the VEGF 936CT polymorphism and stomach cancer.The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene with stomach cancer development was evaluated in a case-control study of 154 Korean stomach cancer patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Our results revealed significant association of T allele-bearing genotypes with increased risk for stomach cancer development. Genotype frequencies of the VEGF 936CT polymorphisms were significantly different between patient and control groups (CT, AOR: 2.007, 95% CI: 1.277-3.156, TT, AOR: 4.790, 95% CI: 1.174-19.539, CT+TT, AOR: 2.147, 95% CI: 1.382-3.337). When stratified by gender and age, genotype frequencies were significantly different for stomach cancer in women and in patients younger than 55 years (in women, CT, OR: 3.049, 95% CI: 1.568-5.930, CT+TT, OR: 3.132, 95% CI: 1.638-5.990; in55 years, CT, OR: 3.306, 95% CI: 1.413-7.732, CT+TT, OR: 3.967, 95% CI: 1.729-9.104). In addition, this association partially remained in cases with intestinal and diffuse-type stomach cancer.Our present study suggests that the VEGF 936CT polymorphism is a susceptibility factor for stomach cancer, at least in Korean. These observations, however, require further confirmation by a larger multi-ethnic study.

Angiogenesis is an essential process in the development, growth and metastasis of malignant tumors such as colon cancer. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. A case control study was carried out to determine whether there is an association between the VEGF 936CT polymorphism and colon cancer.DNA samples taken from 262 colon cancer patients and 229 healthy controls were amplified by polymerase chain reaction for the VEGF 936CT polymorphism.Genotype frequencies of the VEGF 936CT polymorphism were significantly different between patient and control groups (CT+TT, odds ratio(OR): 1.524, 95% confidence interval (CI): 1.033-2.249). When stratified by gender and age, the frequencies of the T allele-bearing genotypes significantly increased risk for colon cancer in women and patients younger than 55 years (in women, OR: 1.996, 95% CI: 1.151-3.464 and in55 years, OR: 4.156, 95% CI: 1.885-9.163). In addition, this association remained in most cases with distal and proximal colon cancer.Our study suggests that the VEGF 936CT polymorphism might be a genetic determinant for colon cancer, at least in Koreans.

Purpose To evaluate the safety and efficiency of the Ultrasound (US)-guided large needle core biopsy of axilla lymph nodes. Materials and Methods From March 2004 to September 2005, 31 patients underwent the US-guided core biopsy for axilla lymph nodes. Twenty five lesions out of 31 were detected during breast US, and 6 of 31 cases were palpable. Lymph nodes were classified based on their shape and cortical morphology. The core biopsy of axilla lymph nodes was performed on suspicious lymph nodes found during breast ultrasonography to find out whether the patients had a history of breast cancer or not. Among the 31 patients, 16 patients were associated with breast cancer. The lesion sizes varied from 0.6 cm to 3.3 cm (mean = 1.59 ± 0.76 cm). US-guided core biopsies were performed with 14 G needles with an automated biopsy gun. Total 3 or 5 specimens were obtained. Results Among the 31 cases of axilla lymph nodes core biopsies, 11 cases showed malignant pathology. Seven out of 11 cases were metastatic lymph nodes from breast cancer; 2 cases were from primary unknown and 2 cases from lymphomas. On the other hand, 20 histopathologic results of axilla lesions were benign: subacute necrotizing lymphadenitis (n = 2), dermatopathic lymphadenitis (n = 1), reactive hyperplasia (n = 10) and free of carcinoma (n = 7). Conclusion The US-guided large needle core biopsy of axilla lesions is safe and effective for the pathological evaluation. The core biopsy is believed to be easy to perform if suspicious lymph nodes or mass lesions are found in the axilla.

Microsatellite instability (MSI) has been reported in 25% to 45% of sporadic endometrial carcinoma. The clinicopathologic and molecular characteristics of MSI-high phenotype in colorectal and gastric carcinomas have been widely investigated; however, the clinicopathologic impact of MSI on endometrial carcinomas remained unclear. This study was performed to determine the clinicopathologic and molecular significance of MSI in endometrial carcinomas. We analyzed the MSI status using National Cancer Institute-recommended 5 microsatellite markers, and the immunohistochemical profiles of various regulatory proteins of cell cycle and apoptosis using tissue microarray in 100 endometrial carcinomas. The results were compared between MSI-high and MSI(-) groups as for the traditional clinicopathologic prognostic parameters and the immunoreactivities of various regulatory proteins. We especially focused on the endometrioid type adenocarcinoma to exclude the bias from nonendometrioid type adenocarcinomas with more aggressiveness and a close association with MSI(-) phenotype. The incidence of MSI-high phenotype was significantly higher in endometrioid type than in nonendometrioid serous type (20% vs. 0%, P

The amplification and overexpression of Her2 proto-oncogene have been found to be associated with the development and progression of human breast cancer. A polymorphic valine allele at codon 655 of the Her2 gene (Her2(V655)) was suggested by some authors to be a susceptible genetic factor for the development of breast cancer. The Her2 polymorphism at codon 655 was investigated in 304 Korean women including 177 patients with breast cancer. The association between Her2 genotype and Her2 protein overexpression was also examined in breast cancers by immunohistochemistry. Her2(V655) was not associated with a significant breast cancer risk (odds ratio (OR), 1.792; 95% confidence interval (CI), 0.459-6.991). The frequency of homozygous or heterozygous valine allele increased in stage 2 patients (OR, 1.67; 95% CI, 0.67-4.19), and patients in stages 3 and 4 (OR, 3.36; 95% CI, 0.85-13.42) compared to patients in stage 0. However, an association between the presence of the valine allele and the overexpression of Her2 protein could not be demonstrated. These results suggest that Her2 polymorphism at codon 655 is not associated with the development of breast cancer in Korean women. However, there is a possibility that the valine allele at codon 655 might be related to increased risk of breast cancer progression.

Double primary mucoepidermoid-hepatocellular carcinoma of the liver is extremely rare, and only one case has previously been reported in the literature, although there have been about 14 cases of primary mucoepidermoid carcinoma of the liver. Most of the reported hepatic mucoepidermoid carcinoma showed a poor prognosis. We presently report the second case of a double primary mucoepidermoid carcinoma and hepatocellular carcinoma with a brief review of the published literature. A 52-year-old man was admitted because of epigastric pain that lasted for 2 months. A computed tomography of the abdomen revealed a 7-cm, ill-defined mass with irregular marginal enhancement in the left lobe of liver. Another 2-cm nodular tumor was found in segment 8 of the right lobe. The two separate nodules in the patient's liver demonstrated clearly different histologic and immunohistochemical features. The pathological diagnoses were mucoepidermoid carcinoma and hepatocellular carcinoma for the larger and the smaller tumors, respectively. The patient died of liver failure 6 months after a left lobectomy of the liver.