STMN1 Expression Is Associated with FIGO Grade and Presence of Cervical Involvement 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 PTEN and PI3KCA mutations are common in uterine endometrioid carcinoma (UEC), they do not correlate with FIGO grade. Stathmin (STMN1) regulates microtubule dynamics in cell proliferation. Its expression is associated with activation of the phosphatidylinositol 3-kinase (PI3K) pathway, and its expression has been shown to correlate with grade and other clinicopathologic features in UEC. In this study, we evaluated UEC for expression of STMN1 as a possible prognostic marker.
Design: A tissue microarray was constructed using tumor tissue from 68 cases of UEC grade 1, 66 cases of UEC grade II, and 20 cases of UEC grade III. Samples of proliferative and secretory endometrium were also included in the analysis. STMN1 expression was detected using standard immunohistochemical staining with polyclonal STMN1 antibody (#3352, Cell Signaling). STMN1 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 STMN1 staining score for grade I tumors was 0.6 (σ=0.13), grade II was 1.01 (σ=0.16), and grade III was 2.36 (σ=0.25). Tumors that invaded the cervix had an average STMN1 score of 1.5 (σ=0.13) while tumors without cervical involvement had an average STMN1 expression of 0.9 (σ=0.13), p=.025. There was no statistically significant correlation between STMN1 staining and other histological/clinical tumor attributes including depth of invasion, lymph node metastasis, or mucinous tumor phenotype.
Conclusions: In this study, we demonstrate that STMN1 expression is significantly different between FIGO grades in UEC with increased mean levels of expression in higher FIGO grades. Additionally, tumors with cervical involvement have statistically significant levels of STMN1 staining. The association between STMN1 expression and FIGO grade suggests that alterations in the PI3K pathway downstream of PI3K activation could correlate to increasingly aggressive tumor phenotype. Given the association between STMN1 expression and cervical invasion, STMN1 may serve as a molecular marker of direct local extension rather than distant metastatic spread. Future directions include examining STMN1 expression as a predictive marker of response to microtubule inhibitors in endometrial carcinoma.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 8:45 AM
Platform Session: Section E, Monday Morning