GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis.

BACKGROUND: Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance. METHODS: GLUT1 glucose transporter immunostaining was studied in normal colon and benign colon adenomas and in 112 colorectal carcinomas from patients for whom long term clinical outcome was known. RESULTS: GLUT1 immunostaining was absent in normal colorectal epithelium and tubular adenomas, and absent or only weakly apparent in tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1 immunostaining. Tumors from 92 patients had low GLUT1 expression (< 50% of cells were GLUT1 positive) and 19 of these patients (21%) died of disease during follow-up. In contrast, tumors from 20 patients had high GLUT1 expression (> 50% of cells were GLUT1 positive) and 9 of these patients (45%) died of disease during follow-up. Disease specific mortality was greater in patients with high GLUT1 tumors (relative risk of 2.4; P=0.02). In a multivariate analysis to assess whether high GLUT1 staining correlated with increased mortality independently of Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1 staining was 2.3 times that in the group with low GLUT1 staining, a difference that approached statistical significance (P=0.07). CONCLUSIONS: GLUT1 glucose transporter expression is associated strongly with neoplastic progression in the colon, and assessment of the extent of GLUT1 immunostaining in colorectal carcinoma identifies patients with a poorer prognosis.

GLUT1 glucose transporter expression in benign and malignant thyroid nodules.

Malignant cells exhibit increased rates of glycolysis and glucose uptake, the latter of which is mediated by glucose transport proteins. Because several types of cancer have been shown to express high levels of the GLUT1 glucose transporter isoform, we hypothesized that expression of GLUT1 might distinguish malignant from benign thyroid tissue. Archival thyroid tissue obtained at surgery was immunostained for GLUT1 protein. There were 38 benign cases (24 follicular adenoma, 1 Hürthle cell adenoma, 8 nodular goiter, 3 Hashimoto's thyroiditis, 2 Graves' disease) and 28 cases of thyroid cancer (17 papillary and its follicular variant, 6 follicular, 1 Hurthle cell, 2 anaplastic, 2 medullary). Normal thyroid tissue adjacent to nodules showed no thyrocyte staining in any case. No GLUT1 staining was seen in thyrocytes in benign nodular tissue, except for a single case of Hashimoto's thyroiditis in which a few Hurthle cells showed weak staining. Among the thyroid cancers, 13 of 28 (46%) showed tumor cell GLUT1 staining in at least some areas. This included 9 of 17 cases of papillary carcinoma and its follicular variant, 2 of 6 cases of follicular carcinoma and 2 of 2 cases of anaplastic carcinoma. Tumor cell GLUT1 staining was seen in two patterns: circumferential plasma membrane staining focally within the tumor, or asymmetric staining of the basilar aspect of tumor cells adjacent to stroma in some cases of papillary carcinoma. We conclude that GLUT1 expression is frequently detectable by immunostaining in thyroid cancer, but not in benign nodules or normal thyroid. GLUT1 expression may be a clinically useful molecular marker for thyroid cancer.