Originally published as JCO Early Release 10.1200/JCO.2005.01.5180 on December 5 2005

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EZH2 Expression Is Associated With High Proliferation Rate and Aggressive Tumor Subgroups in Cutaneous Melanoma and Cancers of the Endometrium, Prostate, and Breast

From the the Gade Institute, Section of Pathology; Department of Surgical Sciences, University of Bergen; Department of Clinical Medicine, Section of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Department of Biochemistry, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands

Address reprint requests Lars A. Akslen, MD, PhD, Children’s Hospital, Harvard Medical School, Vascular Biology Program, Karp Family Research Labs 12.125, 300 Longwood Ave, Boston, MA 02115-5737; e-mail: lars.akslen{at}childrens.harvard.edu or lars.akslen{at}gades.uib.no

PURPOSE: EZH2 is a member of the polycomb group of genes and important in cell cycle regulation. Increased expression of EZH2 has been associated previously with invasive growth and aggressive clinical behavior in prostate and breast cancer, but the relationship with tumor cell proliferation has not been examined in human tumors. The purpose of this study was to validate previous findings in a population-based setting, also including tumors that have not been studied previously.

PATIENTS AND METHODS: In our study of nearly 700 patients, we examined EZH2 expression and its association with tumor cell proliferation and other tumor markers, clinical features, and prognosis in cutaneous melanoma and cancers of the endometrium, prostate, and breast.

RESULTS: Strong EZH2 expression was associated with increased tumor cell proliferation in all four cancer types. Associations were also found between EZH2 and important clinicopathologic variables. EZH2 expression showed significant prognostic impact in melanoma, prostate, and endometrial carcinoma in univariate survival analyses, and revealed independent prognostic importance in carcinoma of the endometrium and prostate.

CONCLUSION: Our findings point at EZH2 as a novel and independent prognostic marker in endometrial cancer, and validate previous findings on prostate and breast cancer. Further, EZH2 expression was associated with features of aggressive cutaneous melanoma. The fact that EZH2 might identify increased tumor cell proliferation and aggressive subgroups in several cancers may be of practical interest because the polycomb group proteins have been suggested as candidates for targeted therapy. EZH2 expression should, therefore, be further examined as a possible predictive factor.

Supported by Norwegian Cancer Society, Norwegian Research Council, Meltzer Research Fund, and Helse Vest Research Fund.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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