K-ras Mutations in Endometrial Carcinoma of Uterus – Molecular and Morphological Correlation.
Jinjun Xiong, Mai He, Cynthia L Jackson, Virgina Breese, C James Sung, Margaret M Steinhoff, M Ruhul Quddus, W Dwayne D Lawrence. Women & Infants Hospital, Providence, RI; Rhode Island Hospital, Providence
Background: K-ras gene product in the EGFR pathway is critical in the development of many types of malignancy including lung, colon and endometrial cancer. Often, K-ras mutation-associated lung, pancreatic, colon or ovarian cancer display mucinous differentiation. Previous studies showed that K-ras gene mutation can be found in 10-40% of endometrial carcinoma. Endometrial carcinoma includes many histological subtypes with variable pathogenesis. To our knowledge, the correlation of K-ras mutations with carcinoma with significant mucinous differentiation of uterus has not been reported before. The current study is aimed to investigate the prevalence of K-ras gene mutations in the mucinous carcinoma and endometrioid carcinoma with significant mucinous differentiation (MC&ECMD) and compare it with endometrioid carcinoma (EC).
Design: With IRB approval, specimens of MC&ECMDs and ECs were searched from the archival files of the Department of Pathology, W&I Hospital. Thirteen MC&ECMDs and eight ECs were selected for this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections that were macrodissected to ensure more than 80% of tumor cells. PCR amplification for K-ras codons 12 and 13 were performed (RIH, RI), followed by sequencing using capillary electrophoresis (Sequencing Facility, Yale University, CT). The sequencing results were analyzed by “Sequence Scanner v1.0” program.
Results: K-ras codons 12 and 13 mutations were detected in 10 of 13 (76.9%) MC&ECMDs with the most prevalent mutation being G12D (codon 12, GGC > GAC) (4/10, 40%). Only 2 of 8 ECs (25%) were positive for K-ras mutation, all being G12D. Statistically significant difference of K-ras mutation was noted between MC&ECMDs and ECs (P< 0.05, Fisher's exact test). Overall G12 D mutation is the most prevalent mutation detected in this study (6/12, 50%).
Conclusions: Significantly higher prevalence of K-ras mutations was found in the MC&ECMD group compared to the EC group in this study, indicating close association between K-ras mutation and mucinous differentiation, and suggesting possible unique pathogenic pathway for MC&ECMD. Further study of K-ras mutation in MC&ECMD with its clinical application appears warranted.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 155, Wednesday Afternoon