Abstract 5145: Glycolytic gene expression in ER-positive breast cancer tumors: Comparison with metastasis scores

Abstract

Abstract Background: The proliferation genes of metastatic expression scores for ER-positive tumors are thought to be critical. While the correlation between these scores and distant metastasis has clinical utility, further improvements of predicted risk and a better understanding of the underlying biological processes is desirable. Since cell survival, proliferation, and cellular metabolism are integrated, we asked if expressions of the genes of the glycolytic pathway are associated with predicted metastatic risk. Methods: RNA was extracted from 46 breast cancer tumor blocks collected at the Blumenthal Cancer Center with Institutional Review Board approval. A previously described metastasis score (MS) (Tutt et al) consisting of 14 proliferation genes was determined by RT-PCR and with categorization as either high or low risk. These tumors had been previously profiled using Oncotype Dx® and categorized using Oncotype Dx® and TAILORx cut points. Thirteen glycolysis pathway genes (GLUT1, HK1, HK2, PKM1, PKM2, ENO3, LDHA, LDHB, PGK1, PKFFB4, PFKL, PFKM, and KHK) were profiled. Data were analyzed using Eisen's Cluster program. Results: In a preliminary analysis of 46 tumors, we identified 27 tumors that were predicted to be at high risk for distant metastasis based on MS. Clustal analysis of the glycolysis pathway genes divided the tumors into two major groups. Of the 20 tumors that displayed higher levels of glycolytic expression, 19 had a high MS and 1 had a low MS. Of the 26 tumors with lower glycolytic expression, 8 had a high MS and 18 had a low MS. Four of the 20 higher glycolytic expression group were categorized as high risk using Oncotype Dx® cutpoints while 5 were categorized as high risk using TAILORx cutpoints. Of the 26 lower glycolytic expression group, 1 tumor was classified as high risk by either Oncotype Dx® or TAILORx criteria. Seven tumors in each of the higher and lower glycolytic expression groups were classified as intermediate risk with Oncotype Dx® cutpoints;12 and 19 were classified as intermediate risk in the higher and lower glycolytic expression groups, respectively, with TAILORx cutpoints. A 2.5 to 12 fold range in glycolytic gene expression was observed between the tumors; the largest ranges were observed with LDHA, LDHB, PGK1 and PKM1. Discussion: Tumors that were highly proliferative based on MS showed higher expression of the glycolysis pathway genes. However, there was a subset of tumors that displayed discordant proliferative and glycolytic expression. Although the tumors with high MS cluster together, the expression level of the composite genes differ between tumors, suggestive that different pathways may be involved. The predominance of intermediate Oncotype Dx® categorized tumors made the interpretation of association difficult. Studies with clinical outcome data will be required to assess the utility of the inclusion of glycolytic gene expression in predicting metastatic risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5145. doi:1538-7445.AM2012-5145