High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas

Kidani, Kazunori; Osaki, Mitsuhiko; Tamura, Takayuki; Yamaga, Kensaku; Shomori, Kohei; Ryoke, Kazuo; Ito, Hisao

doi:10.1016/j.oraloncology.2008.03.016

« Previous Next »Oral Oncology
Volume 45, Issue 1 , Pages 39-46, January 2009

High expression of EZH2 is associated with tumor proliferation and prognosis in human oral squamous cell carcinomas

Kazunori Kidani
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
- Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, Tottori University, Faculty of Medicine, Yonago, Tottori 683-8503, Japan
- Corresponding author. Address: Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan. Tel.: +81 859 38 6053; fax: +81 859 38 6050.
Mitsuhiko Osaki
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
- Division of Molecular Genetics and Biofunction, Tottori University, Graduate School of Medical Science, Yonago, Tottori 683-8503, Japan
Takayuki Tamura
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Kensaku Yamaga
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Kohei Shomori
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Kazuo Ryoke
- Division of Oral and Maxillofacial Biopathological Surgery, Department of Medicine of Sensory and Motor Organs, Tottori University, Faculty of Medicine, Yonago, Tottori 683-8503, Japan
Hisao Ito
- Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

Received 29 January 2008; received in revised form 17 March 2008; accepted 17 March 2008. published online 14 July 2008.

Summary

Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes and is important in cell cycle regulation. Overexpression of EZH2 protein has been associated with biological malignancy of prostate cancer and several other cancers. The aim of the present study was to evaluate the expression of EZH2 protein in human oral normal mucosa, dysplasia and oral squamous cell carcinoma (OSCC) with clinicopathological profiles. EZH2 expression was assessed by Western blotting and immunohistochemistry in 3 OSCC cell lines, 10 normal mucosae, 50 dysplasias and 102 OSCCs. The labeling indices (LIs) of EZH2, Ki-67, P53, and the apoptotic index (AI) were evaluated by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. Western blot analysis detected EZH2 protein as a single band at 91kDa in the 3 OSCC cell lines, but it was almost absent in non-tumoral oral mucosae. The LI of EZH2 was highest in the OSCCs, followed by the dysplasias (p<0.05) and normal mucosae (p<0.05) with significant difference. The LI of EZH2 correlated with the clinical stage, tumor size, lymph node metastasis and LIs of Ki-67 and P53, but not with the AI in OSCCs, and inversely correlated with the histological differentiation of OSCCs. The survival rate calculated by the Kaplan–Meier method revealed that OSCC patients with higher EZH2 expression showed poorer prognosis than those with a lower EZH2 expression (p<0.01). These results suggest that overexpression of EZH2 is correlated with malignant potential and poor prognosis in OSCCs. EZH2 might serve as a novel biomarker for predicting prognosis in patients with OSCCs.