Expression of metabolism-related proteins in triple-negative breast cancer.

Abstract

To investigate the dominant metabolic type of triple-negative breast cancer (TNBC) and evaluate its clinical implication through analysis of protein expression related to glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation. Tissue samples from 129 patients with TNBC who underwent mastectomy due to invasive breast cancer from 2000 to 2005 were prepared for tissue microarray. By immunohistochemical staining of the tissue microarrays, the markers of glycolysis-related proteins (Glut-1, CAIX, MCT4), glutaminolysis-related proteins (GLS1, GDH, ASCT2), and mitochondrial enzymes (ATP synthase, SDHA and SDHB) were analyzed. Based on the results, the metabolic phenotypes were defined based on positivity for more than two of three markers for each phenotype as follows: glycolysis type (Glut-1, CAIX and MCT4), glutaminolysis type (GLS1, GDH and ASCT2) and mitochondrial type (ATP synthase, SDHA and SDHB). The percentages of samples with metabolic phenotypes of tumor and stroma of TNBC were as follows: for tumor, mitochondrial type (85.3%) > glutaminolysis type (67.4%) > glycolysis type (63.0%); and for stroma, glutaminolysis type (37.2%) > glycolysis type (16.3%) > mitochondrial type (14.0%). The most common metabolic phenotype of TNBC was glycolysis type for basal-like type and non-glycolysis type for non-basal-like type (p=0.047). The correlation between glutaminolysis and mitochondrial type was statistically significant in both tumor and stroma (p<0.001). In conclusion, tumor cells of TNBC express glycolysis and mitochondrial metabolism-related proteins. Glycolysis type is the most common phenotype of basal-like type, and reversely, non-glycolysis type is the most common phenotype of non basal-like type.