mTOR Over-Expression in Recurrent Low Grade Endometrioid Adenocarcinomas
Rebecca Buell-Gutbrod, Sonja Chen, Phui-Ly Liew, M Ruhul Quddus, Joyce J Ou, Cunxian Zhang, W Dwayne Lawrence, C James Sung. Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI; Taipei Medical University, Taipei, Taiwan
Background: Inhibitors of the mammalian target of rapamycin (mTOR) are of interest in the treatment of endometrial carcinoma (EMCA).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. Previous studies have shown over-expression of mTOR in up to 7% of EMCA. The role of mTOR over-expression in recurrent disease has not been established. A biomarker which indicated risk of recurrence could be of clinical utility in guiding early adjuvant treatment (e.g. vaginal cuff radiation). Furthermore, if recurrent disease shows molecular progression, mTOR inhibitors may offer therapeutic benefit.
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, 517(31%) G2, and 224(13%) G3. 87 cases recurred: 27(31%) G1, 27(31%) G2, and 33(38%) G3. Archival paraffin embedded tissue of 24 G1 and 21 G2 with documented subsequent recurrence were examined by IHC for localization and over-expression of mTOR. Age and stage match controls and tissue from recurrent lesions (where available) were evaluated concurrently.
Results: Over-expression of mTOR was seen in 7/24 (29%) G1 tumors which subsequently recurred vs. 13/18 (72%) controls (P=0.01). Of the 10 recurrences tested, 5 showed mTOR over-expression. In 4 of these, the tumor was initially negative for mTOR.
|mTOR (+)||P value|
|G1 (n=24)||7 (29%)||0.01 (G1 vs G1 control); 0.005 (G1 vs. G2)|
|G1 Recurrence (n=10)||5 (50%)|
|G1 Control (n=18)||13 (72%)|
|G2 (n=21)||19 (90%)||0.63 (G2 vs. G2 control)|
|G2 Control (n=16)||13 (81%)|