Gian Franco Zannoni1, Giuseppina Improta2, Angela Pettinato3, Chiara Brunelli1, Giancarlo Troncone4, Giovanni Scambia5, Filippo Fraggetta3. 1. Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy. 2. Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Rionero in Vulture, Italy. 3. Pathology Unit, Cannizzaro Hospital, Catania, Italy. 4. Pathological Section, Department of Public Health, University of Naples Federico II, Naples, Italy. 5. Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: Rachel N Grisham; Kathleen N Moore; Michael S Gordon; Wael Harb; Gwendolyn Cody; Darragh F Halpenny; Vicky Makker; Carol A Aghajanian Journal: Clin Cancer Res Date: 2018-05-29 Impact factor: 12.531