Aims To evaluate the incidence of PI3KCA, KRAS and BRAF mutations in primary ovarian clear cell carcinoma (OCCC).
Methods 63 consecutive patients, with a proven diagnosis of OCCC, according to WHO criteria, were included into the study. Pyrosequencing analysis of all three genes hotspot regions were performed on 2.5 µm sections of formalin-fixed paraffin-embedded tissue from primary OCCC.
Results PI3KCA mutations were found in 20/63 (32%) cases; KRAS mutations were found in 8/63 (13%); no BRAF V600 mutations were found. In particular, 12/20 mutations (60%) of PI3KCA were found in the exon 20, whereas the remaining eight cases presented mutations in exon 9 (8/20; 40%). KRAS pyrosequencing analysis revealed higher incidence of codon 12 mutations (7/8; 90%) than codon 13 mutations (1/8; 10%). In five cases (5/66; 8%), synchronous mutations, affecting PI3KCA and KRAS genes, were found. No differences were found in the distribution of hotspot mutations, according to the stage.
Conclusions The high frequency of PI3KCA mutations, the low rate of mutations in KRAS and the absence of mutations in BRAF, indicate a molecular signature of OCCCs different from other ovarian carcinomas. Detection of driver mutations, such as PI3KCA and KRAS, may be the basis for a targeted therapy, although the clinical and therapeutic implications of these findings have to be supported by further studies.
- OVARIAN TUMOUR
- TUMOUR BIOLOGY
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Handling editor Runjan Chetty
Contributors GI, AP and CB carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. FF, GFZ and GT participated in the design of the study and performed the statistical analysis. FF, GFZ and GS conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.