PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma

Abstract

Dysregulated signaling on the PI3-kinase/Akt cascade is reportedly associated with early stage and favorable prognosis in some kinds of malignancies including breast cancer, endometrial cancer, and colorectal cancer. PIK3CA, a catalytic subunit of PI3-kinase, is known to be activated in ovarian clear cell carcinoma (CCC), which is categorized as type I ovarian cancer. The aim of this study was to investigate the clinical significance of PIK3CA overexpression in the disease. We performed immunohistochemical analyses of PIK3CA, PTEN, p-Akt, p27 and p53 expressions in primary ovarian clear cell carcinomas from 62 Japanese patients. Genetic analyses of PIK3CA mutation and amplification were further conducted. PIK3CA was overexpressed in 45 tumors (73%), PTEN expression was negative in 3 (5%), and p53 was positive in 8 (13%). Overexpressed PIK3CA was found to be associated with p-Akt overexpression (P = .007). PIK3CA overexpression tended to be observed in more of stage I disease (73% versus 47%, P = .07) and was associated with absence of residual tumor at the initial surgery (96% versus 71%, P = .01). Furthermore, survival analyses revealed that PIK3CA overexpression correlated with improved overall survival (P = .03). Subsequent genetic analyses demonstrated that PIK3CA overexpression correlated with the presence of mutation or amplification of the PIK3CA gene in tumors (P = .009). Our observations suggest that the subgroup of ovarian clear cell carcinomas harboring activated PIK3CA seems to have better prognosis possibly due to more indolent biological property compared to tumors without PIK3CA activation. PIK3CA may serve as a biomarker for good prognosis and a possible therapeutic target in this lethal subtype of ovarian cancer.