TY - JOUR
T1 - Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma
AU - Zhou, Jun
AU - Roh, Ju Won
AU - Bandyopadhyay, Sudeshna
AU - Chen, Zhengming
AU - Munkarah, Adnan R.
AU - Hussein, Yaser
AU - Alosh, Baraa
AU - Jazaerly, Tarek
AU - Hayek, Kinda
AU - Semaan, Assaad
AU - Sood, Anil K.
AU - Ali-Fehmi, Rouba
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/2
Y1 - 2013/2
N2 - Objective: 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 its clinical significance in endometrial carcinoma has not been reported. Methods: 202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome. Results: A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p < 0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p < 0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p < 0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p < 0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2 (p = 0.0024), FAK and pFAK (p = 0.0001) was significantly associated with decreased overall survival. Conclusion: The overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.
AB - Objective: 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 its clinical significance in endometrial carcinoma has not been reported. Methods: 202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome. Results: A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p < 0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p < 0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p < 0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p < 0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2 (p = 0.0024), FAK and pFAK (p = 0.0001) was significantly associated with decreased overall survival. Conclusion: The overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.
KW - Deregulation of EZH2 FAK and pFAK
KW - Endometrial carcinoma
KW - Histology subtype
KW - Potential therapeutic targets for treatment
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U2 - 10.1016/j.ygyno.2012.07.128
DO - 10.1016/j.ygyno.2012.07.128
M3 - Article
C2 - 22871469
AN - SCOPUS:84872871280
SN - 0090-8258
VL - 128
SP - 344
EP - 348
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -