Significance of the PIK3CA mutations in the differential diagnosis of ovarian epithelial carcinoma

Background: Ovarian carcinoma, one of the most common gynecological malignancies in Central and Eastern Europe, is characterized by a clinical and genetic heterogeneity with a distinct molecular signature for each histologic subtype. Material and methods: Here, we established the frequency of the PIK3CA mutations and amplifications in 100 FFPE tissues with the initial diagnosis of serous ovarian carcinoma. Accordingly, the diagnostic value of combining morphology with genetic and immunohistochemical testing was estimated in this cohort. Results: The PIK3CA mutations and amplifications were found in 4.1% (4/97) and 7.2% (7/97) of samples, respectively with a higher prevalence in low-grade tumors (p=0.0121). All identified variants were classified as pathogenic missense mutations, located within the PIK3CA mutational hotspots. In the light of the molecular and immunohistochemical results, two tumors with the somatic PIK3CA mutations and strongly positive expression for PI3K and hNF1β were eventually re-classified from serous to clear cell carcinomas after pathological re-evaluation. Conclusions: These findings demonstrate that the PIK3CA mutational screening facilitated establishing an accurate diagnosis of ovarian carcinomas and, more importantly, might allow for personalized treatment optimization. As the PIK3CA mutations result in the PI3K/AKT pathway deregulation, the individuals with the somatic PIK3CA variants may be eligible for personalized targeted therapies with PI3K inhibitors.