Mismatch Repair Status in Recurrent Low Grade Endometrioid Adenocarcinomas
Shaolei Lu, Rebecca Buell-Gutbrod, M Ruhul Quddus, Jinjun Xiong, W Dwayne Lawrence, C James Sung. Rhode Island Hospital, Providence, RI; Women and Infants Hospital, Providence, RI; Warren Alpert Medical School of Brown University, Providence, RI
Background: The majority of EMCA present as early stage low grade tumors. Approximately 75% are cured by surgery with or without radiation therapy. When relapse occurs it frequently involves the vaginal cuff (local relapse) but may also present as pelvic or abdominal disease (regional relapse) or as distant metastasis. While the molecular mechanisms at play in the development of EMCA have received much attention, the role of these biomarkers in recurrent disease has not been established. The loss of mismatch repair (MMR) proteins occurs in 7-40% of EMCA. We hypothesize that MMR protein loss may play a role in EMCA recurrence in low grade lesions.
Design: A retrospective review of all endometrioid EMCA at our institution over a ten year span revealed 1685 cases. Of these, 944(56%) were grade (G) 1. A total of 87 cases recurred; 27(31%) were G1. Sixteen recurred at the vaginal cuff; 5 had regional relapse; and 6 had distant metastasis. Archival paraffin embedded tissue of 6 primary G1 EMCA and their respective vaginal cuff recurrences were examined by IHC for loss of expression of MMR proteins, MLH1, MSH2, MSH6 and PMS2.
Results: Of the 6 primary cases 2 cases (30%) showed loss of MMR proteins MLH1 and PMS2. The recurrent lesions in both cases showed the same molecular alteration with loss of MLH1 and PMS2. Statuses of MSH2 and MSH6 were not altered in both primary and recurrent lesions. Time to recurrence was on average 13.5 months (m) (range 12-15 m) in the cases with loss of MMR and an average of 17.5 m (range 12-21 m) in those with retained expression (P=0.1415).
Conclusions: Recurrence of G1 EMCA is uncommon; 2.9% of G1 EMCA recurred in this 10 year series. Two out of six cases we evaluated showed loss of MMR proteins in the primary tumor and in the recurrence. For these cases recurrence occurred 4 months earlier on average as compared to tumors with retained MMR. Further studies will be needed to elucidate the role of MMR defects in recurrent G1 EMCAs.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 110, Tuesday Morning