Skip Navigation LinksHome > September 2013 - Volume 23 - Issue 7 > Endometrial Carcinomas With Significant Mucinous Differentia...
International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0b013e31829ea82f
Uterine Cancer

Endometrial Carcinomas With Significant Mucinous Differentiation Associated With Higher Frequency of K-ras Mutations: A Morphologic and Molecular Correlation Study

Xiong, Jinjun MD*; He, Mai MD, PhD*; Jackson, Cynthia PhD; Ou, Joyce J. MD, PhD*; Sung, C. James MD*; Breese, Virgina BS; Steinhoff, Margaret M. MD*; Quddus, M. Ruhul MD*; Tejada-Berges, Trevor MD; Lawrence, W. Dwayne MD*

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Abstract

Objectives: K-ras gene product in the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway is critical in the development of certain types of malignancies. K-ras mutation–associated pancreatic and ovarian carcinomas often display mucinous differentiation. Previous studies have shown that k-ras mutation is found in 10% to 30% of endometrial carcinomas. We investigated k-ras mutations in several morphologic subtypes of endometrial carcinomas with particular emphasis on various degrees of mucinous differentiation.

Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue sections. Polymerase chain reaction amplification for k-ras codons 12 and 13 were performed, followed by sequencing using capillary electrophoresis. The Fisher exact test is used to compare the prevalent difference of k-ras mutation among the groups. P < 0.05 was considered significant.

Results: K-ras mutations 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).

Conclusion: The findings suggest that mucinous carcinoma and endometrioid carcinoma with significant mucinous component are more likely to be associated with k-ras mutation. Potential clinical implications of k-ras mutation 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.

© 2013 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.

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