[1017] mTOR Expression Is Not Associated with FIGO Grade in Uterine Endometrioid Carcinoma.

Joanna SY Chan, Lora H Ellenson. NYP Weill Cornell Medical Center, New York City, NY

Background: Endometrial carcinoma is the most common cancer of the female genital tract in the US. Currently, there are few molecular prognostic markers. Our previous research has shown that while phosphatidylinositol 3-kinase (PI3K) mutations are common in uterine endometrioid carcinoma (UEC), they do not correlate with FIGO grade. Mammalian target of rapamycin (mTOR) is a growth regulator associated with activation of the PI3K pathway. Previous studies are discordant in proof of mTOR's use as a prognostic marker. In this study, we evaluated UEC for expression of mTOR, to further evaluate mTOR as a possible prognostic marker.
Design: A tissue microarray was constructed using tumor tissue from 68 cases of UEC grade I, 66 cases of UEC grade II, and 55 cases of UEC grade III. Samples of proliferative and secretory endometrium were also included in the analysis. mTOR expression was detected using standard immunohistochemical staining with rabbit monoclonal mTOR antibody (clone 49F9, Cell Signaling technology). A previously described staining index was calculated as the product of staining intensity (0-3) and extent of staining (1=1-10%, 2=11-50%, 3=51-80%, and 4=81-100%) to grade each sample. Institutional IRB approval was obtained for this study.
Results:

mTOR Expression In Uterine Endometrioid Carcinoma
FIGO GradeAverage mTOR scoreRange of Score
I (n=68)4.6±2.80-12
II (n=66)6.2±3.51-12
III (n=55)5.8±3.20-12


The average mTOR staining score for grade I tumors was 4.6 (σ=2.8), grade II was 6.2 (σ=3.5), and grade III was 5.8 (σ=3.2). There was a diversity of staining patterns regardless of FIGO grade as indicated by the range of scores. In benign proliferative endometrium there was moderate diffuse mTOR expression, while secretory endometrium epithelium showed strong diffuse mTOR expression.
Conclusions: In this study mTOR expression did not have a significant association with grade in UEC. Of note, previous studies from our laboratory did not find significant association of either PTEN or PIK3CA mutations with grade. It should be noted that mTOR was expressed in non-neoplastic proliferative and secretory endometrium. Further studies to determine the association of mTOR expression with other prognostic factors and correlation with molecular genetic alterations (e.g., PIK3CA and PTEN) are needed to determine the utility of this putative biomarker.
Category: Gynecologic & Obstetrics

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 165, Wednesday Afternoon

 

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