PIK3CA amplification associates with resistance to chemotherapy in ovarian cancer patients

Abstract

PI3K/AKT signalling pathway controls important cellular processes such as the cell proliferation and apoptosis. PIK3CA gene encoding a catalytic subunit of the PI3K is mutated and/or amplified in various neoplasms, including ovarian cancer. We aimed to evaluate PIK3CA alterations and their clinical importance in ovarian cancer patients. Molecular analysis was performed on 117 ovarian carcinomas with the use of qPCR, SSCP and sequencing. In a group of 98 patients with complete clinical data, 62 patients were treated with standard taxane-platinum regimens and 36 patients with platinum-cyclophosphamide regimens. A multivariate analysis was performed by the Cox’s and logistic regression models. PIK3CA mutations occurred in 5/117 (4.3%) carcinomas, exclusively in the endometrioid and clear cell types (P=0.0002); they were also associated with low FIGO stage (P=0.0003), low tumor grade (P=0.045) and early patient’s age at diagnosis (P=0.0005). The PIK3CA amplification (predominantly a low-level) was found in 28/117 (24%) ovarian carcinomas. It was more frequent in TP53 mutant tumors (P=0.012) and tended to associate with high pAKT expression (P=0.061). The PIK3CA amplification strongly diminished odds of complete remission (OR=0.25, P=0.033) and platinum sensitive response (PS, OR=0.12, P=0.004) in the taxane-platinum treated patients. The odds of PS were also much lower in all patients with the PIK3CA amplification evaluated together, regardless of the treatment applied (OR=0.18, P=0.001). Our results suggest that PIK3CA amplification may be a marker predicting ovarian cancer response to chemotherapy.