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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*

International Journal of Gynecological Cancer: September 2013 - Volume 23 - Issue 7 - p 1231–1236
doi: 10.1097/IGC.0b013e31829ea82f
Uterine Cancer

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.

*Department of Pathology, Women & Infants Hospital of Rhode Island, Brown University, †Molecular Laboratory, Department of Pathology, Rhode Island Hospital, Brown University, and ‡Department of Obstetrics and Gynecology, Women & Infants Hospital of Rhode Island, Brown University, Providence, RI.

Address correspondence and reprint requests to Jinjun Xiong, MD, Department of Pathology, Women & Infants Hospital of Rhode Island, 101 Dudley St, Providence, RI 02905. E-mail:

This work was supported in part by a pilot project fund from the Department of Pathology, Warren Alpert Medical School of Brown University.

A portion of the results has been presented at the USCAP Annual Meeting in San Antonio, Texas, in March, 2011.

The authors declare no conflicts of interest.

Received September 10, 2012

Accepted June 3, 2013

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