Overexpression of the Human Erythrocyte Glucose Transporter Occurs as a Late Event in Human Colorectal Carcinogenesis and Is Associated with an Increased Incidence of Lymph Node Metastases1

Energy metabolism of human colon cancer in vivo relies predominantly on glucose. Although studies have revealed increased expression of Glut! mRNA in colon cancer, Glut! protein (Glut!) expression in the large intestine and its significance are still unknown. The objective of this work was to determine whether Glut! is present in human cobrectal neoplasms and whether that presence is of biological significance. Formalin-fixed, paraffin-embedded tissue sections of 53 cobonic adenocarcinornas, 82 adenomas, 46 hyperplastic polyps, and 38 normal colon samples were immunostained with the anti-Glut! antibody MYM. The localization was carried out using the avidin-biotin immunoperoxidase technique. No Glut! immunoreactivity was present in normal colonic mucosa or in hyperplastic pobyps, whereas 8 (10%) of 82 adenomas showed such immunoreactivity. The frequency of Glut! expression in adenomas increased with vilbous morphology and with the size of the adenoma. Forty-four (83%) of 53 colorectal adenocarcinomas expressed Glut!, and, of these, tumors in which >50% of the cancer cells expressed Glut! had a significantly higher incidence of metastasis to the lymph nodes (P = 0.0001). It is concluded that (a) Glut! is expressed as a late event in the carcinogenesis process in human colorectal cancer, and (b) expression of Glut! in a high proportion of cancer cells is associated with a high incidence of lymph node rnetastases.