Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma

An analysis of 63 patients

Gian Franco Zannoni, Giuseppina Improta, Angela Pettinato, Chiara Brunelli, Giancarlo Troncone, Giovanni Scambia, Filippo Fraggetta

Research output: Contribution to journalArticle

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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 mm 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.

Original languageEnglish
JournalJournal of Clinical Pathology
DOIs
Publication statusAccepted/In press - May 6 2016

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Carcinoma
Mutation
Codon
Exons
Incidence
Mutation Rate
Paraffin
Formaldehyde
Genes
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Zannoni, G. F., Improta, G., Pettinato, A., Brunelli, C., Troncone, G., Scambia, G., & Fraggetta, F. (Accepted/In press). Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma: An analysis of 63 patients. Journal of Clinical Pathology. https://doi.org/10.1136/jclinpath-2016-203776

Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma : An analysis of 63 patients. / Zannoni, Gian Franco; Improta, Giuseppina; Pettinato, Angela; Brunelli, Chiara; Troncone, Giancarlo; Scambia, Giovanni; Fraggetta, Filippo.

In: Journal of Clinical Pathology, 06.05.2016.

Research output: Contribution to journalArticle

Zannoni, Gian Franco ; Improta, Giuseppina ; Pettinato, Angela ; Brunelli, Chiara ; Troncone, Giancarlo ; Scambia, Giovanni ; Fraggetta, Filippo. / Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma : An analysis of 63 patients. In: Journal of Clinical Pathology. 2016.
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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 mm 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.",
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N2 - 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 mm 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.

AB - 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 mm 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.

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