Expression and mutation of p53 in tumor effusion cells of patients with ovarian carcinoma: response to cisplatin-based chemotherapy.

p53 alterations are considered as one of the most important factors responsible for drug resistance in ovarian carcinomas, although the relationship between p53 gene status and response to cisplatin-based chemotherapy in ovarian cancer patients remains unclear. The aim of the study was to evaluate the relationship between p53 protein accumulation, p53 gene mutation and response to cisplatin-based chemotherapy in patients with ovarian carcinoma considering conventional clinicopathological parameters. Tissue sections and corresponding cyst and/or ascitic fluid cells from 79 patients with epithelial ovarian cancer were analyzed immunohistochemically for p53 expression. The PCR-SSCP analysis was performed in 25 cases and the results were compared with immunohistochemical data. It was demonstrated that p53 expression reaching approximately 50% of positive cells in immunostaining was usually associated with PCR-amplified exons showing abnormal migration and suspected for mutation. p53 gene changes were not correlated with histological structure, grade of differentiation or residual tumor after cytoreductive surgery, despite being detected more frequently in III/IV than in II FIGO stages and in patients with residual disease above 2 cm. A significant correlation between p53 accumulation and p53 gene alteration and poor response to cisplatin-based chemotherapy was shown. The overall survival time of patients decreased with an increase in p53 protein expression. A strong p53 expression especially accompanied by p53 changes detectable by PCR-SSCP analysis appears to be a good indicator of the resistance to cisplatin-based chemotherapy. The association between strong p53 overexpression and shorter overall survival time was also revealed.