title: Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Karmanos Cancer Center, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Ju-Won
authors.initials: JW
authors.lastname: Roh
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Chen
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Yaser
authors.initials: Y
authors.lastname: Hussein
authors.forename: Baraa
authors.initials: B
authors.lastname: Alosh
authors.forename: Tarek
authors.initials: T
authors.lastname: Jazaerly
authors.forename: Kinda
authors.initials: K
authors.lastname: Hayek
authors.forename: Assaad
authors.initials: A
authors.lastname: Semaan
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein; D004789:Enzyme Activation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis*; D015996:Survival Rate; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human