Enhancer of zeste homolog 2 expression is associated with metastasis and adverse clinical outcome in clear cell renal cell carcinoma: a comparative study and review of the literature.
BACKGROUND
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase mediating chromatin condensation and epigenetic modulation, is overexpressed in various human carcinomas and is associated with adverse clinicopathologic characteristics and biologic behavior. The expression of EZH2 in renal cell carcinomas (RCCs) has not been fully characterized yet.


OBJECTIVE
To evaluate the prognostic role of EZH2 in RCC by analyzing the immunohistochemical staining pattern of the marker in relation to pathologic features and clinical outcome.


METHODS
We correlated the immunolabeling of EZH2 with multiple clinicopathologic features, including Fuhrman nuclear grade, pathologic stage, metastatic status, and clinical outcome in 223 clear cell RCCs (CRCCs) and 21 papillary RCCs, by using tissue microarrays of primary and metastatic cases.


RESULTS
Most CRCCs (75%) showed positive EZH2 staining, with most primary tumors showing focal staining in comparison to nonfocal staining in metastatic cases. In primary tumors, EZH2 expression was associated with higher nuclear grade and lower pathologic stage. Metastatic tumors showed a higher number of positive cases (81% versus 67%) and a more diffuse and more intense pattern of staining than primary CRCCs. For the 22 locally advanced primary tumors (T3/4) and 43 metastatic RCCs, patients who experienced RCC-related deaths significantly overexpressed the marker in comparison to patients who did not experience RCC-related mortality.


CONCLUSIONS
By showing that EZH2 expression is associated with increased metastatic potential and a worse clinical outcome, this study suggests that EZH2 can serve as a prognostic biomarker for RCC, thus confirming it as a key molecule driving oncogenesis and metastasis.
From the Departments of Pathology (Drs Xu and Brimo) and Urology (Drs Abourbih, Kassouf, Mansure, Aprikian, and Tanguay), McGill University Health Centre, Montreal, Quebec, Canada; and the Department of Pathology (Dr Sircar), The University of Texas Maryland Anderson Cancer Center, Houston.
Bin
B
Xu
Samuel
S
Abourbih
Kanishka
K
Sircar
Wassim
W
Kassouf
Jose Joao
JJ
Mansure
Armen
A
Aprikian
Simon
S
Tanguay
Fadi
F
Brimo
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011792:Quebec; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2