Abstract 2275: GP88 (progranulin) tissue expression correlates with increased risk of recurrence for estrogen receptor positive invasive ductal carcinoma
Authors: Serrero Ginette , Hawkins Douglas M. , Yue Binbin , Bejarano Pablo , Ioffe Olga , Phillips Jeffrey , Head Jonathan F. , Elliott Robert L. , Kamimura Sayuri 
Published: June 2012

Background: GP88 (progranulin) is a growth/survival factor previously characterized in our laboratory as a critical player of breast tumorigenesis and in the acquisition of resistance to anti-estrogen therapy in estrogen receptor positive (ER+) breast cancer. Previously reported pathological study showed that GP88 was preferentially expressed in ductal carcinoma rather than lobular carcinoma. THe highest expression was found in invaisve ductal carcinoma whereas normal mammmary tissue and benign lesions were negative. The present study examines the prognostic significance of GP88 and the association of GP88 expression with recurrence risk for breast cancer patients with ER+ invasive ductal carcinoma.

Methods: Tissue GP88 expression was determined by immunohistochemistry using Oncostain 88 Kit on formalin-fixed paraffin embedded tissue sections followed by scoring by pathologists. Tumor GP88 expression was then correlated to survival outcomes in two retrospective multi-sites studies. The first training trial established the GP88 cut off value that is associated with decreased disease-free and overall survivals. The second study validated the GP88 cut off value and examined GP88 prognostic value compared to other prognostic factors in multivariate analysis.

Results: The training trial demonstrated that GP88 expression was associated with a highly significant increase in the risk of recurrence of patients with ER+ invasive ductal carcinoma (IDC). This training trial established a GP88 cut-point where GP88 score of 3+ was associated with decreased disease-free and overall survivals. An independent validation study was performed with 264 distinct ER+ IDC cases to verify the strong impact of GP88 on survival outcomes and carry out multivariate analysis. The results confirmed the GP88 cut-point previously established with the training trial and showed that GP88 3+ was associated with a 4-fold higher hazard of disease recurrence when compared with GP88 &lt; 3+ (GP88=0, 1+ or 2+). In addition, patients whose tumors had GP88=3+ showed a 2-fold higher mortality hazard when compared with the lower GP88 group. Multivariate analysis showed that GP88 was an independent risk predictor even after taking into account lymph node status, tumor size, tumor grade, and disease stage.

Conclusion: The data show that the expression of the survival factor GP88 in breast tumor tissue is a prognostic factor, predictive of risk of recurrence and increased mortality for breast cancer patients with early stage ER+ IDC, independent from other prognostic markers. These results provide support for measuring GP88 tissue expression for newly diagnosed early stage breast cancer patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2275. doi:10.1158/1538-7445.AM2011-2275