Overexpression of Enhancer of Zeste Homolog 2(EZH2) and Focal Adhesion Kinase (FAK) – In High Grade Endometrium Carcinoma
Jun Zhou, Sudeshna Bandyopadhyay, Zhengming Chen, Yaser Hussein, Baraa Alosh, Tarek Jazaerly, Kinda Hayek, Rouba Ali-Fehmi. Karmanos Cancer Center, Wayne State University, Detroit, MI
Background: It has been reported that the deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and the clinical significance of such an association in endometrial carcinoma has not been reported.
Design: 202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into subtype (Type I and Type II). TMAs were developed as per established procedures. EZH2, FAK, pFAK immnuohistochemical stain were performed and expression was scored as negative (0), low (1) and high (2).
Results: A total 141 cases (69.8%) Type I tumors and 61 cases (30.2%) type II tumors were identified. The expression of EZH2 and FAK was detected in 68. 8% and 46.1% of tumors, respectively, while pFAK was expressed in 64.7% of tumors. EZH2 overexpression was identified in 7.56% of type I tumors vs. 62.96% of type II tumor (p<0.001). FAK and pFAK overexpression was only seen in 24.79 % and 1.68% of Type I tumors as compared to 72 % and 58.82% of type II tumors respectively (p<0.001). There was a positive correlation between the expression of EZH2, FAK and pFAK (p<0.0001 for all paired association). The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrium invasion and cervical involvement (all p values <0.01). Kaplan-Meier curves showed that overexpression of EZH2 (Log-rank test, p=0.0024), FAK and pFAK (p=0.0001) were significantly associated with decreased overall survival. On multivariate analysis including the overexpression of EZH2, FAK and pFAK, tumor stage, tumor type, vascular invasion and tumor grade, only high tumor grade persisted as an independent prognostic factor for poor overall survival.
|Type I (%)||Type II (%)||p-value|