Phosphatidylinositol-4, 5-biphosphate 3-kinase, catalytic subunit alpha (PI3KCA) and microsatellite instability in ovarian clear cell carcinoma, clinical correlation

Background

Ovarian carcinoma represents a heterogeneous group of diseases. Clear cell carcinoma (CCC), an infrequent subtype, presents particular clinical characteristics and genetic profiles. PIK3CA mutations (PIK3CAmut) in CCC represent the highest frequency among all of the cancer types and a potential treatment target. High microsatellite instability (MSI-H) is known to have a prognostic value in some malignant diseases.

Methods

From a retrospective four-institutional CCC database with cases ranging from 1997 to 2015, 55 ovarian CCCs were analyzed for MSI status and PI3KCAmut and correlated with clinical outcome. A central pathology review was performed. MSI analysis was performed using a conventional PCR method with specific primers for NR27, NR21, NR24 BAT26 and BAT25 mononucleotidic markers and fragment analysis. The PIK3CAmut were detected by real time PCR, using COBAS platform and a specific detection kit from Roche (Cobas® PIK3CA Mutation Test).

Results

Fifty-five cases were analyzed for MSI-H and 33 cases for PIK3CAmut, two of them were not evaluable for both variables and four more were not evaluable for MSI. Main characteristics included: median age 50 years, FIGO stages I-II 63.4%, FIGO III-IV 36.6% of cases. Molecular features analyzed were: 15.38% (8) had MSI-H and 24.24% (8) had PIK3CA mut. Both events were mutually exclusive. Type of PIK3CAmut included: five H1047X, two E545X and one C420R. MSI-H was identified in stage I-II: 10.52% compared to 13.63% in advanced stages without statistical significance. With a median follow up of 58 months, there was no correlation between MSI-H or PIK3CAmut and relapse, survival, platinum resistance or thromboembolic events. PIK3CAmut had a significant correlation with endometriosis (p:0.026) and with early stages FIGO I-II (p: 0.04).

Conclusions

In our series, around 25% of CCC had a PI3KCA mut. This mutation was correlated with initial stage disease (I-II) and endometriosis antecedent. Even if MSI-H was infrequent, both molecular events were mutually exclusive. This study was realized with the support of the Jan B. Vermorken Grant from GEICO.

Clinical trial identification

Legal entity responsible for the study

Fundación Instituto Valenciano de Oncología

Funding

Grupo Español de Investigación en Cancer de Ovario

Disclosure

All authors have declared no conflicts of interest.