KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis

Abstract

The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis-negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively). This may be explained by relatively small sample sizes in earlier studies but could also reflect difficulties in accurately classifying high-grade ovarian malignancies. In the current study, we investigated KRAS and BRAF mutations in 78 low-grade (FIGO grade 1 and 2) endometrioid adenocarcinomas and compared the results with the presence of endometriosis in the tumor-associated ovary and/or in other pelvic sites. KRAS mutations were identified in 12 (29%) of 42 endometriosis-associated endometrioid adenocarcinomas with satisfactory analysis but in only 1 (3%) of 29 tumors in which endometriosis was not identified. BRAF mutation was identified only in a single endometriosis-associated case. These findings support the hypothesis that endometriosis-associated and independent endometrioid adenocarcinoma may develop via different molecular pathways and that KRAS mutations have an important role only in the former tumors. In contrast, BRAF mutations do not appear to have a significant role in either endometrioid adenocarcinoma subgroup. This may be relevant to future targeted therapies in patients with high-stage or recurrent disease and indicate that histopathologists should carefully examine endometrioid adenocarcinoma specimens, including nonneoplastic tissues, for the presence of endometriosis.