000372: CONSISTENT ABSENCE OF BRAF MUTATIONS IN CERVICAL AND ENDOMETRIAL CANCER DESPITE KRAS MUTATION STATUS

Mutational activation of KRAS and BRAF proto-oncogenes, contributes to the development of many human cancers. In view of the paucity of data on their mutation status, we performed a systematic molecular study in 114 clinically and histologically well-defined malignant tumors of uterine cervix and endometrium and correlated the mutation status of KRAS and BRAF with the age at diagnosis, and with tumor grade, stage or histological type. In endometrial cancer, four KRAS mutations were found at codon 12 and two mutations at codon 13, while no mutation was detected at codon 61. Most of the mutations occurred in clinical stage I and in the endometrioid adenocarcinoma subtype. We also detected 3 KRAS point mutations (6.4%) in the 47 cervical cancer samples, two at codon 12 and one at codon 13, while there was no mutation at codon 61. On the contrary, no mutation was identified in BRAF exon 15 for either endometrial or cervical cancer samples at position V600, which represents the most frequently mutated site of BRAF in human cancer. There was no association between KRAS mutations with either histological type, tumor grade or clinical stage. Interestingly however, KRAS mutation status in endometrial cancer was strongly associated with increased age at diagnosis (P , 0.001). Our data conclusively document a) the absence of BRAF mutations in gynecological cancer, despite the mutation status of KRAS, b) suggest that KRAS mutations reflect an early event in endometrial carcinogenesis and c) imply that BRAF activation is involving alternative pathways in gynecological cancer.