P2-12-32: Association between Progranulin (GP88) Expression and Recurrence Risk for Breast Cancer Patients with Estrogen Receptor Positive Invasive Ductal Carcinoma.

Abstract

Purpose: GP88 (progranulin) is a critical player of breast tumorigenesis for estrogen receptor positive (ER+) breast cancer. Pathological studies showed that GP88 was expressed in invasive ductal carcinoma (IDC), but not in normal mammary tissue, benign lesions or lobular carcinoma. The present study examines GP88 prognostic significance in association with recurrence risk for patients with ER+ IDC. Patients and Methods: Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis in paraffin-embedded tumor tissues in correlation with patients’ survival outcomes. The training study established a GP88 cut-off value associated with decreased disease-free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut-off value and compared GP88 prognostic information with other prognostic factors in multivariate analysis. Results: GP88 expression is associated with a statistically significant increase in recurrence risk for ER+ IDC patients. The training study established that GP88 3+ score by IHC analysis was associated with decreased DFS (p=0.0004) and OS (p=0.0036). The independent validation study verified that GP88 3+ score for the high risk group and demonstrated that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88<3+. GP88 remained an independent risk predictor after considering age, nodal status, tumor size, tumor grade, progesterone receptor expression, treatment and disease stage. Conclusion: Our training and validation studies demonstrate that the survival factor GP88 is a prognostic biomarker, predictive of recurrence risk and increased mortality for ER+ IDC patients, independent from other prognostic factors. These results provide support for measuring GP88 tissue expression for newly diagnosed early stage breast cancer patients. This work was supported by grants R43CA124179, and U01CA113916 from the National Cancer Institute, grants 07-2007-064 and 02-2010-010 from the Avon Foundation for Women. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-32.