This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Collett, K. Articles by Akslen, L. A. Search for Related Content PubMed PubMed Citation Articles by Collett, K. Articles by Akslen, L. A.

Expression of Enhancer of Zeste Homologue 2 Is Significantly Associated with Increased Tumor Cell Proliferation and Is a Marker of Aggressive Breast Cancer

Authors' Affiliations: ¹ Section for Pathology, The Gade Institute; ² Centre for Clinical Research; Departments of ³ Radiology and ⁴ Surgery, Haukeland University Hospital; ⁵ Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway; and ⁶ Department of Biochemistry, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands

Requests for reprints: Lars A. Akslen, Section for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. Phone: 47-55973173; Fax: 47-55973158; E-mail: lars.akslen{at}gades.uib.no.

The polycomb group protein enhancer of zeste homologue 2 (EZH2) has been linked to invasive properties of aggressive breast cancer. In this report, tissue microarray analysis of 190 breast carcinomas from a nested case-control study shows that EZH2 is significantly associated with interval breast cancers. Further, a strong relationship was found with tumor cell proliferation (by Ki-67 expression), locally advanced disease, metastasis at presentation, markers of the basal epithelial phenotype (positivity for cytokeratin 5/6 or P-cadherin), and p53 status. EZH2 expression was also significantly associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype. For prediction of aggressive disease (any event of locally advanced disease, lymph node spread, or distant spread), EZH2 was the only variable of significance in multivariate analysis, whereas no additional information was given by Ki-67. Although EZH2 expression was significant in univariate survival analysis, only tumor cell proliferation and lymph node status were significant in the final multivariate model. In conclusion, our findings indicate an important relationship not only between EZH2 and markers of tumor cell proliferation but also with aggressive disease. These findings might be practically important and relevant because the polycomb group proteins have recently been suggested as candidates for targeted therapy.

This article has been cited by other articles:

				V. K. Rajasekhar and M. Begemann Concise Review: Roles of Polycomb Group Proteins in Development and Disease: A Stem Cell Perspective Stem Cells, October 1, 2007; 25(10): 2498 - 2510. [Abstract] [Full Text] [PDF]

				A. Miremadi, M. Z. Oestergaard, P. D.P. Pharoah, and C. Caldas Cancer genetics of epigenetic genes Hum. Mol. Genet., April 15, 2007; 16(R1): R28 - R49. [Abstract] [Full Text] [PDF]

				W. Fiskus, M. Pranpat, M. Balasis, B. Herger, R. Rao, A. Chinnaiyan, P. Atadja, and K. Bhalla Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells Mol. Cancer Ther., December 1, 2006; 5(12): 3096 - 3104. [Abstract] [Full Text] [PDF]

				L. Ding and C. G. Kleer Enhancer of Zeste 2 as a Marker of Preneoplastic Progression in the Breast Cancer Res., October 1, 2006; 66(19): 9352 - 9355. [Abstract] [Full Text] [PDF]