Expression of Bcl-2 and the antiapoptotic BAG family proteins in ovarian cancer.

In epithelial ovarian cancer (EOC), literature on the prognostic value of B-cell lymphoma 2 (Bcl-2) is limited and inconsistent. Little is known about the expression patterns and the prognostic value of prosurvival proteins of the Bcl-2-associated athanogene (BAG) family proteins interacting with Bcl-2. The major aim of this study was to further define the expression pattern and the prognostic role of Bcl-2 together with BAG-1, BAG-3, and BAG-4 proteins in EOC patients receiving platinum/taxane-based chemotherapy. A tissue array was constructed comprising 63 EOC patients. The expression and the prognostic value of Bcl-2, BAG-1, BAG-3, and BAG-4 in EOC were evaluated by immunohistochemistry and multivariate analysis. A positive cytoplasmic staining for Bcl-2 was observed in 23.8% of EOC samples and in all histologic subtypes. BAG-1, BAG-3, and BAG-4 were detected in tumor cell nuclei and cytoplasm. Interestingly, all patients presenting with a positive Bcl-2 staining showed additional positive nuclear and cytoplasmic BAG-4 expression (P=0.014). Expression of Bcl-2, or the BAG family proteins, independent of nuclear or cytoplasmic localization, had no significant impact on either disease-free or overall survival, both in univariate and multivariate survival analyses with the limitation of a small cohort of cases. In this study, no association between Bcl-2 expression in EOC tumor tissue and prognosis was found. Similarly, nuclear and cytoplasmic expression of the prosurvival proteins of the BAG family had no significant impact on patients' outcome.

Expression of epidermal growth factor receptor and vascular endothelial growth factor in vaginal squamous cell cancer.

OBJECTIVE: Primary invasive squamous cell carcinoma of the vagina is a rare neoplasm. Investigations concerning the potential of new therapeutic targets are limited. STUDY DESIGN: A total of 34 patients with primary invasive squamous cell carcinoma of the vagina was identified, who were treated at our institution between 1994 and 2008. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression was assessed using immunohistochemistry from paraffin-embedded tissue blocks. RESULTS: EGFR was expressed in 33 of 34 (97.1%) and VEGF was expressed in 12 of 34 cases (35.3%). There was no statistically significant relationship between clinicopathologic parameters (clinical stage, grading, tumor size), patient survival, and EGFR and VEGF expression. CONCLUSION: VEGF was moderate and EGFR was frequently expressed in invasive squamous cell carcinoma of the vagina. In our sample size, immunohistochemical staining was not statistically significantly associated with prognosis.

p16INK4a expression in invasive vulvar squamous cell carcinoma.

p16, a member of the INK4a family of cyclin-dependent kinase inhibitors, is known as a negative regulator of cell cycle progression and differentiation. Although p16 has been shown to be a promising biomarker for the detection of cervical intraepithelial neoplasia, few data have been published on vulvar cancer. Using immunohistochemistry, we evaluated the expression of p16 in 80 cases of invasive vulvar squamous cell carcinoma. Results were correlated with clinicopathologic parameters and survival data to determine the prognostic significance of p16 in vulvar cancer. p16 expression was detected in 34 of 80 (43%) cases of invasive vulvar squamous cell carcinoma. The expression was localized to the cytoplasm and the nuclei of the tumor cells. Correlations between p16 expression status and any clinicopathologic variables failed to be of statistical significance. In a univariate analysis, groin lymph node status, tumor stage, and tumor grade were associated with disease-free and overall survival, respectively. Patients positive for p16 expression showed a significantly longer disease-free and overall survival by univariate analysis. p16 expression was not associated with survival in a multivariate Cox-regression model. Our data add on those published in the literature and suggest that p16 may be of prognostic significance in invasive vulvar squamous cell carcinoma.

The lack of laminin-5 as a prognostic marker in low-grade cervical squamous intraepithelial lesions: correlation with clinical follow-up data.

Low-grade cervical squamous intraepithelial lesions have a high rate of spontaneous regression but may undergo surgical treatment (cone biopsy) in case of persistence of the lesion or discrepancy between Pap-smear diagnosis and biopsy diagnosis. This may sometimes lead to surgical complications and/or adverse effects on fertility. Thus, the present study was designed to investigate the potential of laminin-5 as a sensitive molecular marker identifying cervical intraepithelial neoplastic lesions (CIN), which are likely to regress and ultimately spare women unnecessary surgical procedures. Cervical punch biopsy samples from 65 women with either a CIN I or a CIN II were evaluated for the expression of laminin-5 by immunohistochemistry. All study subjects agreed to a conservative clinical management and were frequently followed-up (median follow-up time 237 days) to evaluate for changes in the dysplastic lesion. Laminin-5 staining results were correlated with patient's characteristics as well as clinical follow-up data. Laminin-5 expression was detected in 16 of 40 CIN I (40%) lesions, 2 of 21 CIN II (9.5%) lesions and none of 4 reclassified CIN III lesions. Within positive cases, laminin-5 expression was localized to the cytoplasm of the dysplastic cells. The laminin-5 expression was significantly associated with the grade of CIN lesion (p < 0.005). Correlations with patient's characteristics were not statistically significant except for education and ectocervical smear diagnosis. No significant associations were noted between laminin-5 expression and either regression, persistence or progression of the CIN lesions. These data indicate that laminin-5 is not a useful diagnostic adjunct in histopathology for the identification of CIN lesions with progressive capacity.