Abstract 677: Progranulin/GP88 tumor tissue expression further stratifies survival outcomes of patients classified by their Nottingham Prognostic Index

Abstract

Abstract Background: The Nottingham Prognostic Index (NPI) combines nodal status, tumor size and histological grade and is used to provide predictive value information on survival for patients with primary breast cancer. Attempts to improve the performance of NPI have been carried out by inclusion of other factors, such as biomarker expression as well as addition of other structural features such as vascular invasion. In the present study, we investigated whether expression of the survival factor GP88 (progranulin), known to be overexpressed in breast cancer, would improve NPI’s predictive value. GP88/Progranulin is an 88 kDa autocrine growth and survival factor that is overexpressed in estrogen receptor positive (ER+) invasive ductal carcinoma (IDC) in association with resistance to anti-estrogens and aromatase inhibitor while the cells remain ER+. Previous training and validation pathological studies totaling 600 cases of ER+ IDC had demonstrated that GP88/Progranulin tissue expression was an independent prognostic marker od recurrence and mortality for early stage ER+ IDC. Methods: We examined by immunohistochemistry the GP88 tumor tissue expression of 508 formalin fixed paraffin embedded cases of ER+ IDC with known clinical outcomes and for which NPI had been determined. GP88 IHC expression was scored by two board certified pathologists and classified into two score groups of GP88 < 3+ (0, 1+, 2+) and GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) and overall survival outcomes (OS) was then examined by Kaplan Meier analysis, Cox proportional Hazard ratio and Pearson’s X2 test. Results: Patients were categorized into three NPI groups (< 3.4, 3.4-5.4, >5.4). Kaplan-Meier survival graphs of cases categorized by their NPI scores and GP88 expression showed that for each NPI subgroup, patients having tumors with a high GP88 expression (GP88 IHC score of 3+) had a worse DFS than patients within the same NPI subgroup with low GP88 expression (GP88 IHC score < 3+). When adjusted for NPI, high GP88 score was highly significantly associated with recurrence. Its hazard ratio is 3.30 (95% CI 2.12 to 5.14). Conclusions: These data suggest that the determination GP88 tumor expression at time of diagnosis for early stage breast cancer patients could provide additional survival information than the ones provided by NPI alone that maybe useful for improving the risk management of patients. Citation Format: Ginette Serrero, Douglas Hawkins, Olga Ioffe, Pablo Bejarano, Binbin Yue. Progranulin/GP88 tumor tissue expression further stratifies survival outcomes of patients classified by their Nottingham Prognostic Index [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 677. doi:10.1158/1538-7445.AM2017-677