Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder.
OBJECTIVE
The Polycomb group gene, EZH2, functions as a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies, including prostate, breast, and lymphoma. We evaluated EZH2 mRNA and protein expression in bladder specimens from patients and the EZH2 mRNA expression in five bladder cancer cell lines.


METHODS
EZH2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR) in 38 bladder tissue specimens. We also evaluated 39 bladder cancer specimens for EZH2 protein expression using immunohistochemistry with affinity-purified antibodies to human EZH2. In addition, five human bladder cancer cell lines were analyzed by RT-PCR for EZH2 mRNA expression.


RESULTS
Five of 14 (36%) nontumor bladder specimens versus 21 of 24 (88%) bladder tumors showed EZH2 mRNA expression (P=0.003). All of the invasive tumors (10 of 10) had detectable EZH2 mRNA expression, compared with 11 of 14 (79%) superficial tumors. In addition, EZH2 mRNA expression was noted in 100% (16 of 16) of high-grade bladder tumors versus 50% (4 of 8) of low-grade tumors (P=0.01). EZH2 protein expression, meanwhile, was increased in neoplastic tissue compared with nontumor urothelium (78% versus 69% of nuclei, P<0.005). There were no differences in EZH2 protein levels between superficial and invasive tumors. High-grade tumors had increased EZH2 staining compared with normal urothelium (78% versus 68%, P<0.005), whereas low-grade lesions did not. Four of five human bladder cancer cell lines expressed high levels of EZH2, whereas only low levels were detected in one cell line.


CONCLUSIONS
We report a significant increase in EZH2 expression in transitional cell carcinoma of the bladder compared with normal urothelium. These data suggest that similar to other human malignancies, increased EZH2 expression correlates with oncogenesis of the bladder.
Raman
Jay D
JD
Department of Urology, The New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York 10021, USA.
Mongan
Nigel P
NP
Tickoo
Satish K
SK
Boorjian
Stephen A
SA
Scherr
Douglas S
DS
Gudas
Lorraine J
LJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D001743:Urinary Bladder / Q000737:chemistry / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2