Glucose transporter Glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix

Hypoxic tumors are known to be more malignant, to be more likely to metasta size, and to have a poor prognosis. They are also radio- and chemoresistant , For this reason, it is desirable that a clinically useful marker of hypox ia is found, so that treatment with radiotherapy and bioreductive chemother apy can be rationally applied to individual patients. Glut-1 is a facilitat ive glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intr insic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phasphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven pred ictive qualities, is a suitable gold standard used in our laboratory to val idate new hypoxia markers. Using this technique, pretreatment pO(2) measure ments were performed on 54 patients with locally advanced cervical carcinom a, Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initia tion of treatment, By using a low-tech scoring system, pO(2) was found to c orrelate weakly with Glut-1 score (r = 0.28; P = 0.04). To extrapolate this correlation to the known adverse effects of tumor hypoxia on outcome, we e xamined the prognostic significance of Glut-1 staining in a retrespective s eries of 121 patients, An absence of Glut-1 significantly increased the lik elihood of metastasis-free survival (P = 0.022) but did not significantly e ffect disease-free or recurrence-free survival. These findings suggest that Glut-1 be an intrinsic marker of hypoxia that can easily be applied in a c linical setting.