Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug.

A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-x L , hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients.

No abstract

e13017 Background: Cerebral metastases develop in 10-30% of patients with breast cancer and in around 3.3 to 4% of patients with ovarian cancer. The present study evaluates the expression of ER alpha and beta receptors, PR, HER2 and markers associated with metastases: stromal cell-derived factor-1 (SDF1) and its receptor CXCR4, breast cancer metastasis suppressor (BRMS1), astrocyte elevated gene (AEG-1), depending on the status of BRCA1 protein in cancerous cells of the patients (somatic mutation). Methods: The material originated from 30 women with breast cancer and 22 patients with ovarian cancer in whom cerebral metastases were detected. The studies were conducted on paraffin block sections, the markers were detected using immunocytochemistry, employing specific antibodies. Results: In the breast cancer group, BRCA 1 protein expression was detected in 11 patients, absence of the protein in 19. No significant differences were disclosed in the grade of ER, PR, HER2, SDF1, CXCR4, BRMS1 or AG-1 expression which would be dependent on the status of BRCA1. Expression of the proteins failed to correlate with patients' age, clinical advancement at diagnosis, presence of metastases to lymph nodes. Patients with no PR expression significantly more frequently manifested high expression of CXCR4 (p = 0.0436). The ovarian cancer group included 7 patients with expression of BRCA1 protein, absence of such expression was recorded in 15 patients. No statistically significant differences were disclosed in the expression of the studied factors which would be related to the status of BRCA1 in cancer cells. Also, no differences were detected in the expression of the studied factors which would depend on the patient’s age, primary advancement of the disease or histological type of the cancer. Conclusions: Among numerous molecular factors examined in women with breast or ovarian cancer no statistically significant differences were detected which would depend on BRCA1 protein status in cancer cells. The absence of PR expression in women with breast cancer was associated with high expression of CXCR4, which might indicate that PR-negative women with breast cancer exhibit higher metastatic potential.