Abstract P2-10-40: Correlation between expression of the prognostic marker Progranulin (GP88) with Oncotype Dx Recurrence Score in estrogen receptor positive breast tumors

Abstract

Abstract Background: GP88 (Progranulin, acrogranin) is an 88kDa glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Biological studies have shown that GP88 in ER+ breast cancer cells was associated with estrogen independence and resistance to anti-estrogen therapies and aromatase inhibitors. In addition, GP88 stimulated migration, invasion and angiogenesis, hallmarks of metastasis. Pathological studies have demonstrated that GP88 was preferentially expressed in invasive ductal carcinoma while lobular carcinoma was mostly negative. No expression was found in normal mammary tissue. Two retrospective studies totaling 530 cases of ER+ formalin-fixed paraffin-embedded invasive ductal carcinoma (IDC) established that high GP88 expression was associated with a 4-fold increase in risk of recurrence and 2.5-fold increase in death when compared to low GP88 scores. Multivariate analysis showed that GP88 remains a predictor of recurrence even when adjusted for prognostic factors such as tumor size, grade, stage, lymph node status and age. High level of GP88 was also found to be elevated in the serum of breast cancer patients when compared to healthy individuals. Since GP88 tumor tissue expression appears as a prognostic factor for ER+ breast cancer, we proposed to investigate whether GP88 tumor tissue expression would correlated to Oncotype Dx® Recurrence Score which is now for early stage ER+ node negative breast cancer patients. Methods: Eight five cases from women ages 37–77 with ER+ invasive mammary carcinoma from three different institutions and with an available Oncotype Dx recurrence score were selected with approval from each site's IRB. GP88 expression was determined by immunohistochemistry (IHC) using the anti-human GP88 6B3 monoclonal antibody (A&G) on a Ventana automated staining platform. For all cases examined, GP88 IHC scores (0, 1+, 2+, 3+) were compared to routine clinicopathologic factors (tumor size, grade, and stage), PR, HER2/neu and Ki67 expression (by image analysis) and to their Oncotype DX® recurrence score (Genomic Health). The associations of GP88 with the parameters described above were assessed by t test or ANOVA. Results: The GP88 tissue expression correlated with Oncotype Dx Recurrence score (p < 0.03) as well as with Ki-67 index (p < 0.004). Age, HER2/neu and PR status did not correlate with GP88 expression. Details of these finding will be presented here. Conclusion: This study shows that GP88, an important tumor aggressiveness indicator, significantly correlates with Oncotype DX score and confirms that GP88 correlates with other tumor clinicopathologic parameters and prognostic markers. Further studies are underway to determine whether GP88 in combination with routine markers, particularly Ki67, could be used instead of Oncotype DX Assay to predict outcome and provide information for the management of ER+ breast cancer patients. This study is supported by grant 02–2010-010 from the Avon Foundation for Women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-40.