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Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance

Authors' Affiliations: Departments of ¹ Cancer Biology and ² Pathology, and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts

Requests for reprints: Arthur M. Mercurio, Department of Cancer Biology, University of Massachusetts Medical School, LRB-408, 364 Plantation Street, Worcester, MA 01605. Phone: 508-856-8676; Fax: 508-856-1310; E-mail: arthur.mercurio{at}umassmed.edu.

Purpose: The β4 integrin has been implicated in functions associated with the genesis and progression of carcinomas based on data obtained from cell lines and mouse models. Data on its expression and relevance to human carcinomas, however, are relatively scant. The aim of this study was to assess its expression and prognostic significance in human breast carcinomas.

Experimental Design: We integrated data on β4 expression from multiple gene profiling studies of breast tumors of known clinical outcome with immunohistochemical analysis of 105 breast carcinomas, and we identified genes whose expression correlates with that of β4.

Results: The expression of both β4 mRNA and protein is not homogeneous in breast cancer and it associates most significantly with the "basal-like" subtype of breast tumors (P = 0.008). No association between β4 and HER2 expression was evident from either gene profiling or immunohistochemical analysis. To gain insight into the relevance of β4 expression to human breast carcinomas, we generated a 65-gene "β4 signature" based on integration of four published gene profiling studies that included the top 0.1% of genes that correlated with β4, either positively or negatively. This β4 signature predicted decreased time to tumor recurrence and survival of patients when applied to four data sets including two independent ones.

Conclusions: These observations indicate that β4 expression in human breast cancer is restricted and associated with basal-like cancers, and they support the hypothesis that β4 may function in concert with a discrete set of proteins to facilitate the aggressive behavior of a subset of tumors.