mTOR and STMN1 Expression Is Associated with Type I Endometrial 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. Endometrial carcinoma is broadly classified as Type 1 (low grade carcinoma with endometrioid histology with good prognosis) and Type 2 (high grade carcinoma with serous or clear cell histology with aggressive behavior), which also have different molecular genetic profiles. Our previous research has shown that Type 1 cancers have gene mutations in both PTEN and PIK3CA, however Type 2 cancers are associated with only PIK3CA gene mutations. Mammalian target of rapamycin (mTOR) and stathmin (STMN1) expression are associated with activation of the phosphoinositide 3-kinase (PI3K) pathway. In this study, we evaluated Type 1 and Type 2 endometrial carcinomas for expression of mTOR and STMN1 for use as possible prognostic markers.
Design: A tissue microarray was constructed using tumor tissue from 153 cases of Type 1 carcinoma (FIGO 1=68, FIGO 2=65, FIGO 3=20) and 34 cases of Type 2 carcinoma (serous type). Samples of proliferative and secretory endometrium were also included in the analysis. mTOR and STMN1 expression were detected using standard immunohistochemical staining with rabbit monoclonal mTOR antibody (clone 49F9, Cell Signaling) and polyclonal STMN1 antibody (#3352, Cell Signaling). Expression was scored by extent of staining (0=absent, 1=<10%, 2=10-50%, 3=>50%). Institutional IRB approval was obtained for this study.
Results: The average mTOR staining score for Type 1 tumors was 2.1(σ=0.17), while the average mTOR score for Type 2 tumors was 1.7(σ=0.10). The average STMN1 staining score for Type 1 FIGO 3 tumors was 2.4 (σ=0.3), while the average STMN1 score for Type 2 tumors was 0.94 (σ=0.24). This difference in staining score between Type 1 and Type 2 endometrial tumors was statistically significant with p < 0.05. Neither STMN1 nor mTOR staining scores were significantly different when samples were evaluated for other tumor characteristics including depth of invasion or lymph node involvement.
Conclusions: Type 1 endometrial carcinoma revealed higher mTOR and STMN1 staining scores than Type 2. In STMN1 staining, this difference is only seen in Type 1 FIGO grade 3 tumors; however, the association between mTOR staining and Type 1 carcinoma was independent of FIGO grade. The increased mTOR and STMN1 expression may be a reflection of underlying PTEN mutations. Further studies are necessary to address this possibility. mTOR and STMN1 may be useful molecular markers in distinguishing Type 1 versus Type 2 endometrial carcinoma regardless of other confounding factors.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 142, Wednesday Morning