Alterations of the TP53 gene and TP53 protein expression in epithelial ovarian cancer before and after chemotherapy

Background: A role for the TP53 (alias p53) tumor-suppressor gene in chemoresistance has recently been discussed, but little is known about the clinical relevance of the TP53 gene to chemoresistance. To elucidate the relevance of TP53 status to chemoresistance, we investigated the TP53 gene and TP53 protein expression in tumors from the same patients, before and after chemotherapy. Methods: Twenty-one patients with ovarian cancer, who had residual disease after primary surgery, were studied. These patients received chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide, and then underwent a second surgery. Polymerase chain reaction-single strand conformation polymorphism analysis and cycle sequencing were performed to determine TP53 mutation. TP53 protein was detected by Western blot analysis. Results: Of the 21 patients studied, 9 responded to chemotherapy. Mutation of the TP53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation of the gene was observed in 5 patients, all of whom were nonresponders. TP53 protein was detected in 10 patients (3 responders and 7 nonresponders) before chemotherapy. After chemotherapy, the expression of TP53 protein increased in these 3 nonresponders, and became positive in 2 other nonresponders. Conclusions: This study showed for the first time in clinical investigation that alterations to TP53 could develop in association with chemotherapy, and that TP53 status may relate to the mechanisms of chemoresistance in patients with epithelial ovarian cancer.