Tissue expression of the growth factor GP88 is a predictor of recurrence in patients with estrogen receptor positive breast tumors.

Abstract

Abstract Abstract #1088 Background
 Our laboratory is working on the characterization of novel breast cancer targets that have therapeutic an/or diagnostic applications. We have previously identified the growth factor GP88 as a significant player of breast tumorigenesis. GP88 is expressed in human breast cancer cells in a positive correlation with tumorigenesis. In estrogen receptor positive breast cancer cells, GP88 mediates estrogen proliferation effect and its increase is associated with resistance to anti-estrogen therapy. Inhibition of GP88 expression in human breast adenocarcinoma lead to inhibition of tumor incidence and tumor growth in nude mice. Pathological studies showed that ductal carcinoma expressed GP88 whereas benign lesions and normal mammary tissue were negative. Based on this evidence, the present study was carried out to investigate whether high GP88 expression in estrogen receptor positive invasive ductal carcinoma is associated with increased recurrence and decreased overall survival.
 Methods
 Under an IRB approved study, 239 archival formalin-fixed, paraffin-embedded estrogen receptor positive invasive ductal carcinoma with a minimum of 4 years follow-up were obtained from three United States tumor banks The clinical data included patients demographics such as age and race, tumor characteristics including tumor size, tumor grade, nodal status, disease stage and receptor status, time and type of first recurrence, time and status of last follow-up. GP88 expression was determined by immunohistochemistry using Oncostain 88TM IHC kit on five-micrometer sections. GP88 expression was scored as: <10% of cells staining – negative, >10% of cells staining – positive with positive staining graded from weak/focal (1+) to moderate/focal or diffuse (2+) to strong/diffuse (3+). The statistical analysis of GP88 expression in all cases was carried out. The Oncostain 88TM test performance was evaluated for its ability to predict disease-free (DFS) and/or overall survivals (OS) using Kaplan Meier curves and the Cox proportional hazards models for quantification of risk.
 Results
 The data show that ER+ cases with high GP88 expression (3+) had a hazard ratio for OS of 2.29 (95% CI, 1.38-3.78; p< 0.0013) and a HR for DFS of 2.88 (95% CI 1.59-5.24; p<0.0005). GP88 3+ remained highly significant for OS and DFS even when the data were adjusted for covariates such as nodal status, disease stage, tumor grade, tumor size, supporting the findings that GP88 brings independent information on the recurrence risk and overall survival of ER+ invasive ductal carcinoma.
 Conclusion
 This study demonstrates for the first time that high GP88 expression (3+) is a predictor of higher recurrence and increased mortality in ER+ IDC. These data provide a novel biomarker tissue assay (Oncostain 88TM) with prognostic significance in breast cancer.
 This study was supported by grant 1R43 CA 124179-01A1 from the National Institutes of Health. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1088.