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Identification of GATA3 as a Breast Cancer Prognostic Marker by Global Gene Expression Meta-analysis

Departments of ¹ Pathology, ² Urology, ³ Biostatistics, and ⁴ Surgery, and ⁵ The Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan

Requests for reprints: Celina G. Kleer, Department of Pathology, University of Michigan, 3510C MSRB1, 1150 West Medical Center Drive, Ann Arbor, MI 48109. Phone: 734-615-3448; Fax: 734-615-3441; E-mail: kleer{at}umich.edu.

GATA binding protein 3 (GATA3) is a transcriptional activator highly expressed by the luminal epithelial cells in the breast. Here we did a meta-analysis of the available breast cancer cDNA data sets on a cohort of 305 patients and found that GATA3 was one of the top genes with low expression in invasive carcinomas with poor clinical outcome. To validate its prognostic utility, we did a tissue microarray analysis on a cohort of 139 consecutive invasive carcinomas (n = 417 tissue samples) immunostained with a monoclonal antibody against GATA3. Low GATA3 expression was associated with higher histologic grade (P < 0.001), positive nodes (P = 0.002), larger tumor size (P = 0.03), negative estrogen receptor and progesterone receptor (P < 0.001 for both), and HER2-neu overexpression (P = 0.03). Patients whose tumors expressed low GATA3 had significantly shorter overall and disease-free survival when compared with those whose tumors had high GATA3 levels. The hazard ratio of metastasis or recurrence according to the GATA3 status was 0.31 (95% confidence interval, 0.13-0.74; P = 0.009). Cox multivariate analysis showed that GATA3 had independent prognostic significance above and beyond conventional variables. Our data suggest that immunohistochemical analysis of GATA3 may be the basis for a new clinically applicable test to predict tumor recurrence early in the progression of breast cancer. (Cancer Res 2005; 65(24): 11259-64)

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