Clinical Significance of Glucose Transporter 1 (GLUT1) Expression in Human Breast Carcinoma

Abstract

Glucose uptake and glycolytic metabolism are enhanced in cancer cells compared to normal cells and tissues. Increased expression of glucose transporter 1 (GLUT1) has been reported in human malignant cells. The aim of this study is to determine the expression of the facilitative glucose transporter protein GLUT1 in human breast carcinomas and a possible correlation between GLUT1 expression and clinical outcome including disease-free or overall survival. One hundred consecutive formalin-fixed, paraffin-embedded sections of invasive breast carcinomas were evaluated by means of immunohistochemical staining of GLUT1. Forty-seven (47%) of 100 breast carcinomas showed positive staining for GLUT1. Expression of GLUT1 correlated significantly with nuclear grade (P < < < <0.001), estrogen receptor status (P = = = =0.002), and progesterone receptor statusThe mean disease-free survival periods of GLUT1-positive and -negative patients were 47 ± ± ± ±2.4 months and 54.3± ± ± ±1.3 months, respectively (P = = = =0.017). The mean overall survival periods of GLUT1-positive and -negative patients were 48.7 ± ± ± ±2.2 and 56.1 ± ± ± ±1.3 months, respectively (P = = = =0.043).In the multivariate analysis, disease-free survival correlated significantly with GLUT1, tumor size, and lymph node involvement (P = = = =0.043, P = = = =0.014, and P = = = =0.045, respectively). In analysis of overall survival, however, lymph node involvement, tumor size, and nuclear grade were statistically significant (P = = = =0.024, P = = = =0.023, and P = = = =0.003, respectively). Our data suggest that absence of GLUT1 expression significantly increases disease-free survival. These findings demonstrate that GLUT1 expression in breast carcinoma can be a marker of aggressive biological behavior and identifies a worse prognosis in breast carcinoma patients.

Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer

“…GLUT1 expression in tumors also correlates with the survival of patients. In lung, colorectal, ovarian, laryngeal, and breast carcinomas, high levels of GLUT1 or GLUT3 in the tumors were significant indicators of decreased survival (Baer et al, 1997;Ogawa et al, 1997;Younes et al, 1997;Haber et al, 1998;Cantuaria et al, 2001;Kang et al, 2002). GLUT1 staining has also been identified in 25% of hyperplastic breast tissue and 25% of histologically normal breast tissue adjacent to tumors (Alo et al, 2001).…”

“…GLUT1 expression in breast cancer has also been studied extensively (Brown and Wahl, 1993;Younes et al, 1995;Brown et al, 1996;Binder et al, 1997;Alo et al, 2001;Avril et al, 2001;Bos et al, 2002;Brown et al, 2002;Kang et al, 2002;Ravazoula et al, 2003). GLUT1 expression has been correlated with a number of tumor characteristics.…”

“…Another possible explanation for increased glucose uptake by tumors is the expression of other unrecognized GLUTs. Several studies have detected GLUT1 expression in only 50% of breast cancers (Younes et al, 1995;Binder et al, 1997;Kang et al, 2002). Younes et al (1995) postulated that another, previously unrecognized glucose transporter is likely to be responsible for glucose uptake in those breast cancers that do not express GLUT1.…”

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

“…In lung and ovarian tumor, comparative increase in GLUT1 expression was observed in cancer patients with higher grade of malignancy, higher proliferative index and lower degree of differentiation [111,112]. Consistently, GLUT1 expression level reciprocally correlates with survival rate of cancer patients [112][113][114]. Since the expression and regulation of GLUTs are tissue and often cell-specific, expression of some isoforms may only be observed in tumor cells but absent in normal cells.…”

“…Because GLUT1 was exclusively found in human breast cancer biopsies and its expression was strongly associated with tumor grade, proliferation as well as invasiveness [111,120,121], GLUT1 has been proposed to be a new marker for diagnosis and prognosis of human breast cancers, an indication of tumor aggressiveness, and a possible therapeutic target for patients with breast cancer [114,175]. It has been demonstrated that drug mediated inhibition of glucose transport in-creased the effectiveness of several anti-tumor drugs and effectively induced growth arrest and apoptosis in lung, breast cancer and leukemia cell lines [175,176].…”