The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

Abstract

PurposeGlucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas.MethodsWe used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis.ResultsMembranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively).ConclusionGLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Overexpression of Reactive Oxygen Species Scavenger Enzymes Is Associated with a Good Prognosis in Triple-Negative Breast Cancer

“…Basu et al [7] reported that TNBCs are associated with enhanced fluorodeoxyglucose uptake after comparing fluorodeoxyglucose uptake between TNBC and ER+/PR+/HER2− breast tumors. The same findings were later reproduced by two prospective studies showing that high IHC expression of GLUT1, a glucose transporter expressed in most cell types, is significantly correlated with the TNBC phenotype [8,9,10]. …”

Tumor‐suppressive microRNA‐1291 directly regulates glucose transporter 1 in renal cell carcinoma

“…There are 14 GLUT members, of which GLUT1 , the first member of the GLUT family to be identified, is the most extensively studied. GLUT1 was reported originally as a marker of infantile skin hemangioma and overexpression was reported in several types of human cancers, including RCC . Renal cell carcinomas, like many other cancers, are dependent on aerobic glycolysis for ATP production, a phenomenon known as the Warburg effect .…”

Clinicopathological Significance of Dual-Specificity Protein Phosphatase 4 Expression in Invasive Ductal Carcinoma of the Breast

“…It is a genetically and clinically heterogeneous cancer, and the most common histologic subtype is invasive ductal carcinoma, which accounts for 70% to 80% of all breast cancer cases [ 3 ]. There have been advances in understanding carcinogenesis and breast cancer biology; however, treatment problems persist [ 4 ]. Using proven clinicopathological prognostic parameters, various proteins with essential cellular functions have been proposed as potential predictors of breast cancer [ 5 ].…”