Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance.
BACKGROUND
The polycomb group genes Bmi1 polycomb ring finger oncogene (Bmi1) and enhancer of zeste homolog 2 (EZH2) function as transcriptional repressors involved in gene silencing and in the malignant transformation and biologic aggressiveness of several human carcinomas. In the current study, the authors evaluated Bmi1 and EZH2 protein expression in specimens of human nonsmall cell lung cancer (NSCLC).


METHODS
The authors conducted an immunohistochemical assessment of 157 surgically resected NSCLCs to evaluate the correlation between Bmi1 and EZH2 expression and various features, including clinical, clinicopathologic, and biologic characteristics.


RESULTS
Normal bronchial epithelia revealed abundant expression of Bmi1 and sporadic expression of EZH2. Patients who had high EZH2 expression in tumor cells had a poorer prognosis than patients who had low EZH2 expression in tumor cells all pathologic stages of NSCLC (P = .001) and in pathologic stage I NSCLC (P = .006). Multivariate analysis revealed that high EZH2 expression was a independent, unfavorable prognostic factor in patients with pathologic stage I disease (P = .048). High EZH2 expression was correlated significantly with nonadenocarcinoma histology (P = .001), moderate and poor differentiation (P = .001), advanced pathologic tumor classification (P = .02), and high Ki-67 and cyclin E labeling indices (P < .001). Bmi1 expression, in contrast, was not a significant prognostic factor and was not correlated with any clinicopathologic factors other than early pathologic tumor classification.


CONCLUSIONS
Bmi1 and EZH2 had characteristic and distinctive expression in NSCLCs. High EZH2 expression was correlated with tumor aggressiveness and may provide a novel prognostic marker for NSCLCs.
Kikuchi
Junko
J
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Kinoshita
Ichiro
I
Shimizu
Yasushi
Y
Kikuchi
Eiki
E
Konishi
Jun
J
Oizumi
Satoshi
S
Kaga
Kichizo
K
Matsuno
Yoshihiro
Y
Nishimura
Masaharu
M
Dosaka-Akita
Hirotoshi
H
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C069077:BMI1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1