title: Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma.
abstract: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of PIK3CA mutations. In low grade serous ovarian cancer, KRAS and BRAF mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of KRAS, NRAS, and BRAF hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of KRAS in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of NRAF (exons 2, 3, 4) or BRAF (exon 15). The median age of women with a KRAS mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a KRAS mutation occurs in codon 2 exon 2. NRAS and BRAF mutations were not found.
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, Rome, Italy, gfzannoni@rm.unicatt.it.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Improta
authors.forename: Gaia
authors.initials: G
authors.lastname: Chiarello
authors.forename: Angela
authors.initials: A
authors.lastname: Pettinato
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Filippo
authors.initials: F
authors.lastname: Fraggetta
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D000328:Adult; D000368:Aged; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000235:genetics*
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins