Clinical Significance of Human Erythrocyte Glucose Transporter 1 Expression at the Deepest Invasive Site of Advanced Colorectal Carcinoma

Abstract

Objective: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). Methods: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. Results: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke’s stage (Duke’s <D, 32% vs. Duke’s D, 51%). In the central portion and superficial part, there were no significant differences between Glut1, Ki-67 expression and clinicopathological findings. Glut1 expression at the deepest invasive site correlated significantly with the Ki-67 labeling index. In cases of curative surgery, patients with Glut1-positive lesions at the deepest invasive site showed a significantly poorer prognosis than those with Glut1-negative lesions. Multivariate analysis with logistic regression for 5-year survival in patients who had undergone curative surgery showed that lymph node metastasis and Glut1 expression were significant risk factors. Conclusion: These results indicate that Glut1 expression at the deepest site of tumor invasion can be a useful predictor of a high malignant potential and poor prognosis in advanced CRC.

Oxygen and glucose consumption in gastrointestinal adenocarcinomas: Correlation with markers of hypoxia, acidity and anaerobic glycolysis

“…(22) Overexpression of glucose transporters in the cellular membranes of colon and gastric cancer cells is a frequent event. (11,23,24) A very high glucose consumption was evident in six of 19 cases examined, and these showed a significant overexpression of HIF1α and marginally of HIF2α, the key factors regulating the transcription of glycolytic enzymes and glucose transporters. (3,7,25) This is also in accordance with Positron Emission Tomography (PET) scan data showing glucose uptake by tumors.…”

Prognostic Significance of Volume-based Metabolic Parameters by 18F-FDG PET/CT in Gallbladder Carcinoma

“…According to a study on breast cancer, 18 F-FDG uptake was influenced by the amount of metabolically active tumor cells, and the depth of invasion is associated with Glut-1 expression. Additionally, a positive correlation among increased incidence of lymph node, metastases and Glut-1 expression was seen in patients with gastrointestinal carcinoma [23][24][25][26][27]. When the cancer stage increases, SUV representing glucose uptake increases.…”

Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays

“…Both the present and previous studies show that a relatively large proportion of colorectal tumors express Glut-1. However, in previous studies variation of Glut-1 expression with depth of invasion was shown to be an important determinant of prognosis in early stage tumors (Furudoi et al, 2001, Sakashita et al, 2001, highlighting the point that any array design must include representative samples of this parameter as well as different histological subtypes. The T-Pr array adequately reflected the lack of Glut-1 expression observed in previous studies involving conventional immunohistochemical analysis of prostate tumors.…”