title: Molecular status of PI3KCA, KRAS and BRAF in ovarian clear cell carcinoma: an analysis of 63 patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Rionero in Vulture, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Improta
authors.affiliation: Pathology Unit, Cannizzaro Hospital, Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Pettinato
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Brunelli
authors.affiliation: Pathological Section, Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Pathology Unit, Cannizzaro Hospital, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Fraggetta
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D010053:Ovary / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012384:Rome / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D003062:Codon; C117307:KRAS protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D014157:Transcription Factors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: GENETICS; OVARIAN TUMOUR; TUMOUR BIOLOGY