ATL: A Morphologic and Molecular Correlation Study

Abstract

ObjectivesK-rasgene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies.K-rasmutation–associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown thatk-rasmutation is found in 10% to 30% of endometrial carcinomas. We investigatedk-rasmutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation.MethodsGenomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification fork-rascodons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference ofk-rasmutation among the groups.P< 0.05 was considered significant.ResultsK-rasmutations were detected in 8 (80%) of 10 mucinous carcinomas, 12 (67%) of 18 endometrioid carcinomas (ECs) with significant mucinous differentiation (ECMD), 4 (25%) of 16 ECs, and 1 (9%) of 11 serous carcinomas. The differences were statistically significant between mucinous carcinomas versus EC (P< 0.01) and ECMD versus EC (P< 0.05).ConclusionThe findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated withk-rasmutation. Potential clinical implications ofk-rasmutation lies in the management of recurrent or higher-stage endometrial mucinous tumors, which would not be responsive to treatment protocols containing epidermal growth factor receptor inhibitors.