K-ras Mutations in Mucinous Lesions of Uterus
Mai He, Cynthia L Jackson, Virginia Breese, Margaret M Steinhoff, Jinjun Xiong, W Dwayne Lawrence. Brown University/Women Infants Hospital, Providence, RI; Brown University/Rhode Island Hospital, Providence, RI
Background: K-ras mutations are often seen in malignancies of lung, pancreas, colon or ovary displaying mucinous differentiation. Our previous study showed that K-ras mutation can be found in approximately 70% of mucinous carcinoma and endometrioid carcinoma with significant mucinous differentiation (MC&ECMD), significantly higher than other types of endometrioid carcinoma (EC). Current study expanded the mutation study to the mucinous lesions of uterus in order to gain further understanding of the molecular nature and characteristics of these lesions.
Design: With IRB approval, seven “atypical mucinous (endometrial) hyperplasia (AMH)”, six “mucinous (endometrial) metaplasia (MM)” and nine “microglandular hyperplasia of cervix” were obtained from the archival files of the Department of Pathology. Previous MC cases with mutations served as positive control. Six normal cervical biopsy materials were used as negative control. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections that were microdissected to ensure more than 80% of lesional cells. PCR amplification for K-ras codons 12 and 13 were performed and followed by sequencing using capillary electrophoresis. The sequencing results were analyzed by “Sequence Scanner v1.0” program.
Results: K-ras codons 12 and 13 mutations were detected in 5 of 7 (71.4%) AMH, significantly higher than reported in literature (P=0.005, compared to Feng YZ et al., 2005). One of the six (16.7%) MM presented with K-ras mutation. No K-ras mutations were detected in normal cervical material or microglandular hyperplasia. These results provided a significant difference of K-ras mutation between AMH and MG of cervix (P=0.005, Fisher's Exact Test).
Conclusions: Significantly higher prevalence of K-ras mutations was found in the AMH group compared what has been reported in atypical endometrial hyperplasia in literature. Combined with previous result of high prevalence of K-ras mutations in MC&ECMD, it indicated a close association between K-ras mutation and mucinous differentiation, and suggesting possible unique pathogenic pathway for MC&ECMD. Detection of K-ras mutations in mucinous metaplasia suggested a possible neoplastic process. Significant difference between AMH and MG of cervix provided valuable molecular aid in differential diagnosis, esp., with limited biopsy material.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 128, Tuesday Afternoon