KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants.
OBJECTIVE
Mutations of BRAF, a downstream mediator of K-RAS, have been described in serous borderline tumors of the ovary. Data concerning other types of ovarian tumors are scarce. Therefore, we assessed KRAS and BRAF mutation in a series of more than 100 different ovarian tumors.


METHODS
Paraffin-embedded material, including invasive carcinomas, borderline tumors, benign lesions and implants, was used. BRAF codon 600 in exon 15 and K-RAS codon 12 in exon 2 were analysed.


RESULTS
92 cases (92%), including all serous carcinomas (100%), did not show a mutation of BRAF. Eight cases (8.0%), including five serous borderline tumors (31.25%), contained a mutation. In all serous borderline tumors, codon 600 was affected. The remaining three cases were invasive carcinomas of endometrioid (mutation on codon 600), mucinous (mutation on codon 600) and clear cell (mutation on codon 615) subtype. There was no BRAF mutation in mucinous borderline tumors. Regarding K-RAS, 89 cases (87.25%) did not show an aberration. The 11 positive borderline tumors (10.7%) were of serous (22.2%) and of mucinous type (46.6%). There was a KRAS mutation in a serous and a mucinous invasive carcinoma each. BRAF and K-RAS mutations were mutually exclusive and not seen in implants.


CONCLUSIONS
Mutation of either K-RAS or BRAF is frequent in borderline tumors but is not found in invasive serous carcinomas and is very rare in other invasive subtypes. This supports the notion of different pathological pathways. For the development of extraovarian implants, further studies are observed.
Mayr
Doris
D
Institute of Pathology, Ludwig-Maximilians-University of Munich, Germany. doris.mayr@med.uni-muenchen.de
Hirschmann
Astrid
A
Löhrs
Udo
U
Diebold
Joachim
J
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D018282:Cystadenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
D004273:DNA, Neoplasm; D048493:Proto-Oncogene Proteins B-raf