Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer

• Published in: Clinical cancer research Vol. 12; no. 4; pp. 1168 - 1174
• Main Authors: COLLETT, Karin, EIDE, Geir E, ARNES, Jarle, STEFANSSON, Ingunn M, EIDE, Johan, BRAATEN, Audun, AAS, Turid, OTTE, Ariel P, AKSLEN, Lars A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-02-2006
• Subjects: Analysis of Variance; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Proliferation; DNA-Binding Proteins - biosynthesis; Enhancer of Zeste Homolog 2 Protein; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Ki-67 Antigen - analysis; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Invasiveness; Pharmacology. Drug treatments; Polycomb Repressive Complex 2; Receptors, Estrogen - analysis; Survival Analysis; Transcription Factors - biosynthesis; Tumor Suppressor Protein p53 - analysis; Tumors; Cell proliferation; Mammary gland diseases; Biological marker; Homology; Breast cancer; Malignant tumor; Gene expression; Tumor cell; High malignancy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-1533

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.