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Aims In order to determine whether the expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-κB (NF-κB), is associated with the invasiveness of oral squamous cell carcinoma ( OSCC), this study has attempted to investigate the correlation of the aforementioned markers with the well-established invasive pattern grading score (IPGS) and clinicopathological parameters. Methods and results Specimens from 143 OSCC patients with classified clinicopathological parameters and IPGS were stained immunohistochemically using anti-Tn, sTn and NF-κB antibodies. Our results showed that the expression of both Tn and NF-κB was correlated positively with staging ( P = 0.036; P = 0.015), recurrence ( P < 0.001; P < 0.001) and distant metastasis ( P = 0.005; P = 0.009), as well as with IPGS, while the expression of sTn was correlated inversely. In addition, poor survival was associated with overexpression of Tn and NF-κB but not with expression of sTn. Conclusions Our results indicate that a reciprocal relationship between Tn and sTn expression may serve as a reliable indicator for OSCC prognostic evaluation. In addition, expression of Tn rather than sTn may play an important role in deeply invasive OSCC via regulation of NF-κB signalling. [ABSTRACT FROM AUTHOR]

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A expression in atypical squamous cells of undetermined significance (ASCUS)-categorized Pap smears with follow-up biopsies in order to elucidate their relationships in gynecological pathology. Methods: We studied 66 ASCUS-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay from the cervical swab in each ASCUS-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4, and we analyzed the correlations between HR-HPV viral load in each ASCUS-diagnosed Pap smear and p16 expression of smears with follow-up biopsies. Results: Correlation analyses of the corresponding histological diagnoses from 66 ASCUS-diagnosed Pap smears revealed that 21 (32%) cases had only reactive changes and 45 cases showed cervical intraepithelial neoplasia including LSIL (24 cases, 36%) and HSIL or higher (21 cases, 32%). Tests for HR-HPV viral load revealed 17 (26%) negative cases and 49 (74%) positive cases. Immunostaining showed that 26 cases (39%) were negative and 40 (61%) were positive for p16 expression. Comparative analysis of these two tests indicated consistencies as well as discrepancies. They showed significant differences (P < 0.001) between negative p16 expressions of Pap smears with the presence of reactive lesions in follow-up biopsies and HR-HPV viral load. However, no significant difference (P = 0.739 and 0.606) between p16 expression of Pap smears with the presence of LSIL, HSIL or higher in follow-up biopsies and high HR-HPV viral load was found. In addition, there were significant differences (P < 0.001) in specificity and positive predictive value, but no significant differences were found in sensitivity (P = 0.606) and negative predictive value (P = 0.062) between p16 immunostaining and HR-HPV viral load. Conclusion: The results indicate that there is a close association between weak or strong p16 expressions in ASCUS-categorized smears with the presence of SILs in follow-up biopsies and positive HR-HPV viral loads. Conversely, there is also a clear association between the lack of p16 expression and the absence of significant lesions in follow-up biopsies, but this is not consistent with a negative HR-HPV viral load. It is concluded that p16 expression is an indicator of pathogenic activity of HR-HPV, which is an objective biomarker for clarification of ASCUS-categorized Pap smears in gynecological cytopathology. Furthermore, through comparative analysis, directly visualized p16 immunostaining on smears appears to be a more effective method than HR-HPV viral load for the detection of reactive changes and LSILs from ASCUS-categorized Pap smears. [Copyright &y& Elsevier]

Beyond human papillomavirus (HPV) infection, host genetic factors may contribute to cervical carcinogenesis. This study aims to test the hypothesis that CA-dinucleotide repeat polymorphism in the first intron of the interferon-gamma ( IFN-γ) gene is associated with HPV-initiated cervical carcinogenesis. A hospital-based case-control study including patients with low-grade squamous intraepithelial lesions (LSILs; n = 93), high-grade squamous intraepithelial lesions (HSILs; n = 123) and invasive carcinomas ( n = 153) of the uterine cervix, as well as 1:1 age-matched controls, was conducted. The IFN-γ genotype was determined by PCR and capillary electrophoresis with internal standards. HPV genotype was determined by consensus PCR and reverse line blot hybridization. Genotypes containing the 12 or 14 allele (12 or 14 CA repeats) were significantly more common in patients with HSILs than in controls (46% vs. 22%; OR = 3.0; 95% CI = 1.7-5.2; p < 0.0001). In contrast, genotypes containing 13 and 18 were significantly more common in controls than in patients with HSILs (76% vs. 53%; OR = 0.3; 95% CI = 0.2-0.6; p = 0.0001) or squamous cell carcinomas (74% vs. 63%; OR = 0.6; 95% CI = 0.4-1.0; p = 0.037). The frequency of the 12 and 14 genotypes increased significantly in accordance with the severity of cervical carcinogenesis ( p [ABSTRACT FROM AUTHOR]

: ObjectiveThis study aimed to verify one of the major diagnostic dilemmas in routine Papanicolaou (Pap) smears. Atypical squamous cells of undetermined significance (ASCUS) were tested immunocytochemically for p16INK4A (p16), and results were correlated with follow-up biopsies for more accurate diagnoses.: MethodsThe study included 66 Pap smears of ASCUS diagnostic categories, all of which were correlated histologically. The cytological diagnoses of ASCUS were further classified cytologically according to the 2001 Bethesda System, as “atypical squamous cells of undetermined significance (ASC-US)” or “atypical squamous cells which cannot exclude HSIL (ASC-H).” All Pap smears were decolorized and immunostained with the primary anti-p16 antibody, clone E6H4. Immunoreactivity for p16 was correlated with histological sections (which were also immunostained for comparison) in a semiblind fashion.: ResultsOf the 66 smears containing ASCUS, 47 (71%) were reclassified as ASC-US and 19 (29%) as ASC-H. Follow-up biopsies revealed that 21 (32%) cervices had no obvious abnormalities but only reactive changes. A significant proportion of histological diagnoses were CIN1/LSIL (24 cases, 36%), CIN2 or 3/HSIL (17 cases, 26%), squamous cell carcinoma (two cases, 3%), or AIS/adenocarcinoma (two cases, 3%). The p16 immunocytochemical stain was reactive in 40 (60.6%) of 66 smears: either weakly/sporadically (18 cases, 45%) or strongly positive (22 cases, 55%). Conversely, 26 (39.4%) of the smears were negative for p16 and displayed predominantly reactive changes. However, five cases of LSIL and one of HSIL were negative for p16. From the results of p16 immunoreactivity of atypical cells for detection of biopsy-proved significant lesions (HSIL or higher), this analysis was highly sensitive (sensitivity, 95%) and specific (specificity, 96%) and had favorable positive (91%) and negative (98%) predictive values.: ConclusionOn the basis of both morphological and immunostaining patterns, there is a clear association between strong p16 immunostaining of atypical cells in the smears and the presence of significant lesions in the cervix, except in two patients. Similarly, there is a clear association between the lack of p16 expression and the absence of cervical lesions. The p16 immunocytochemical stain can be applied successfully to conventional Pap smears and may serve as a useful biomarker in ASCUS-containing smear diagnoses. This may offer a more objective parameter to help clarify this ambiguous area in gynecological cytopathology. [Copyright &y& Elsevier]

Abstract: Objective.: This study was to correlate high-risk human papillomavirus (HR-HPV) viral load to p16INK4A (p16) expression in atypical glandular cell (AGC)-categorized Pap smears with follow-up biopsies for elucidating their relationships. Methods.: We enrolled 36 AGC-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay in each AGC-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4. Correlations between HR-HPV viral load in each AGC-diagnosed Pap smear and p16 expression of smears with follow-up biopsies were performed. Results.: Comparative analysis of two tests disclosed both consistencies and discrepancies. There were significant differences (P = 0.02) between negative or weak p16 expression of Pap smears with the presence of reactive lesion or LSILs/CIN1s in follow-up biopsies and negative HR-HPV viral load. However, no significant difference (P = 0.317) was found between p16 expression of Pap smears with the presence of HSIL/CIN2, 3 and AIS or adenocarcinoma in follow-up biopsies and high HR-HPV viral load. In addition, there were significant differences (P = 0.012) in specificity, but no significant differences were found in sensitivity (P = 0.604), positive and negative predictive value (P = 0.066 and 0.264) between p16 immunoexpression and HR-HPV viral load. Conclusions.: Pathogenic activity of HR-HPV was indicated by p16 expression on smears and tissue sections, which appears to be a better strategy than HR-HPV viral load test for the detection of clinically insignificant lesions from AGC-categorized Pap smears. [Copyright &y& Elsevier]

Purpose: To present a case of salivary gland malignancy initially mimicking Bell's palsy., Case Report: A 75-year-old woman with hypertension visited our neurological outpatient department,complaining of persistent right facial paralysis for more than a year after oral glucocorticoid therapy with recent development of vertigo and unsteady gait. She was previously diagnosed as having Bell's palsy and was prescribed oral glucocorticoid. However, her right facial muscles were still completely paralyzed, with no signs of improvement. The patient visited the outpatient department of neurology for 3 weeks, seeking treatment for the recent onset of vertigo and ataxia. Brain contrast magnetic resonance imaging (MRI) revealed the right mastoid air cells to be filled with high T2 signal intensity and low T1 signal, with destruction of the bony structure of mastoid, extending to the right jugular bulb. Results obtained from excisional biopsy and pathological analyses were used to diagnose the patient with adenoid cystic carcinoma of the salivary gland. The patient then received a thorough cancer workup and chemoradiotherapy, with the malignancy being under control. However, after a 1-year follow-up, the patient still had permanent right facial palsy., Conclusion: Salivary gland malignancy should be considered in patients with acute and subacute facial nerve paralysis, in addition to Bell's palsy. Brain imaging with contrast agents should be performed for differential diagnosis.

Dysregulation of epidermal growth factor receptor (EGFR) has been associated with colorectal cancer, but no evidence shows a relationship of EGFR expression to clinicopathological parameters in colorectal cancer in Taiwan. Immunohistochemical analysis of EGFR, Ki67, and p53 was performed in tissue microarray slides of 9 normal glandular tissues and 150 specimens including 49 well, 58 moderately, and 43 poorly differentiated colorectal adenocarcinomas. Differences in intensity of EGFR immunostaining and the percentages of Ki67 and p53 positive cells between normal and tumor specimens were evaluated using the Student t-test, one-way ANOVA, and linear regression analysis. Intensity of EGFR staining was weak and nuclear expression of Ki67 and p53 was scattered in all 9 control specimens. Expression of Ki67 and p53 but not EGFR was significantly higher in more advanced grades and TNM stages of colorectal adenocarcinoma than in normal controls. The percentages of Ki67 and p53 stained tumor cells were significantly higher in moderately (Ki67: 60.3 ± 6.5, p53: 47.6 ± 3.8) and poorly (Ki67: 61.8 ± 5.3, p53: 55.1 ± 4.1) differentiated tumor cells than in well differentiated (Ki67: 40.8 ± 4.4, p53: 39.8 ± 4.2) tumor cells. Additionally, the Ki67 and p53 staining intensity was also significantly correlated with the more advanced T, N and American Joint Committee on Cancer (AJCC) clinical stage of colorectal adenocarcinoma, suggesting their usefulness as biomarkers of colorectal adenocarcinoma progression. In conclusion, EGFR immunochemistry may not be a good method for pre-treatment evaluation of colorectal adenocarcinoma in Taiwan.

Gliosarcoma is a very rare primary neoplasm of the central nervous system classified as a variant of glioblastoma. Cortactin, fascin and survivin have been found in several human cancers to play important roles in tumor progression, but the expression pattern of these biomarkers in gliosarcoma is unclear. Immunostaining for cortactin, fascin and survivin was assessed in 6 surgical specimens of brain gliosarcoma, and the relationship between the expression of these biomarkers and tumor size or clinical parameters were examined. Five of our six patients with gliosarcoma survived 3-17 months. One patient is still alive for more than 24 months. The mean immunostaining scores for cortactin were significantly higher in the gliomatous (score 236.6 +/- 45.4) and sarcomatous (score 233.3 +/- 51.4) components than in normal brain tissues (score 21.6 +/- 6.6). The mean cytoplasmic immunostaining scores for fascin and survivin were also significantly higher in the gliomatous and sarcomatous components than in normal brain tissues. In addition, survivin was also stained in the nucleus of tumor cells. Linear regression analysis showed that fascin score in the gliomatous component was significantly associated with tumor size (R = 0.69) and the fascin score in the sarcomatous component was significantly associated with patient's age (R = 0.87). In addition, the survivin cytoplasmic scores in the gliomatous and sarcomatous components were inversely associated with tumor size. Our results demonstrated that over-expression of cortactin, fascin and survivin is associated with malignant transformation of brain gliosarcoma. Development of drugs that target cortactin, fascin and survivin expression may be therapeutic to patients with gliosarcoma.

Objective: This study was to correlate high-risk human papillomavirus (HR-HPV) viral load to p16(INK4A) (p16) expression in atypical glandular cell (AGC)-categorized Pap smears with follow-up biopsies for elucidating their relationships., Methods: We enrolled 36 AGC-categorized Pap smears with subsequent follow-up biopsies. HR-HPV viral load was determined by Hybrid Capture II assay in each AGC-diagnosed Pap smear. Both smears and biopsies were immunostained with a primary anti-p16 antibody, clone E6H4. Correlations between HR-HPV viral load in each AGC-diagnosed Pap smear and p16 expression of smears with follow-up biopsies were performed., Results: Comparative analysis of two tests disclosed both consistencies and discrepancies. There were significant differences (P=0.02) between negative or weak p16 expression of Pap smears with the presence of reactive lesion or LSILs/CIN1s in follow-up biopsies and negative HR-HPV viral load. However, no significant difference (P=0.317) was found between p16 expression of Pap smears with the presence of HSIL/CIN2, 3 and AIS or adenocarcinoma in follow-up biopsies and high HR-HPV viral load. In addition, there were significant differences (P=0.012) in specificity, but no significant differences were found in sensitivity (P=0.604), positive and negative predictive value (P=0.066 and 0.264) between p16 immunoexpression and HR-HPV viral load., Conclusions: Pathogenic activity of HR-HPV was indicated by p16 expression on smears and tissue sections, which appears to be a better strategy than HR-HPV viral load test for the detection of clinically insignificant lesions from AGC-categorized Pap smears.

Beyond human papillomavirus (HPV) infection, host genetic factors may contribute to cervical carcinogenesis. This study aims to test the hypothesis that CA-dinucleotide repeat polymorphism in the first intron of the interferon-gamma (IFN-gamma) gene is associated with HPV-initiated cervical carcinogenesis. A hospital-based case-control study including patients with low-grade squamous intraepithelial lesions (LSILs; n = 93), high-grade squamous intraepithelial lesions (HSILs; n = 123) and invasive carcinomas (n = 153) of the uterine cervix, as well as 1:1 age-matched controls, was conducted. The IFN-gamma genotype was determined by PCR and capillary electrophoresis with internal standards. HPV genotype was determined by consensus PCR and reverse line blot hybridization. Genotypes containing the 12 or 14 allele (12 or 14 CA repeats) were significantly more common in patients with HSILs than in controls (46% vs. 22%; OR = 3.0; 95% CI = 1.7-5.2; p < 0.0001). In contrast, genotypes containing 13 and 18 were significantly more common in controls than in patients with HSILs (76% vs. 53%; OR = 0.3; 95% CI = 0.2-0.6; p = 0.0001) or squamous cell carcinomas (74% vs. 63%; OR = 0.6; 95% CI = 0.4-1.0; p = 0.037). The frequency of the 12 and 14 genotypes increased significantly in accordance with the severity of cervical carcinogenesis (p(test for trend) = 0.0002), whereas the 13 and 18 genotypes showed the opposite trend (p(test for trend) = 0.007). Comparing IFN-gamma genotype and HPV status, 18-containing genotypes were more frequently found in HPV(+) LSILs, and 12-containing genotypes were less frequently found in HPV(+) HSILs. Compared with non-13 genotypes, 13 genotype HSILs were more frequently infected with HPV58 (70% vs. 45%) and less frequently infected with HPV18 (0% vs. 16%; p= 0.007). Genetic polymorphism of the IFN-gamma gene is associated with individual susceptibility to cervical carcinogenesis. This polymorphism correlates with HPV infection in a disease- and type-specific manner., ((c) 2004 Wiley-Liss, Inc.)