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Microregional Expression of Glucose Transporter-1 and Oxygenation Status: Lack of Correlation in Locally Advanced Cervical Cancers

Authors' Affiliations: ¹ Institute of Physiology and Pathophysiology, University of Mainz and ² Department of Obstetrics and Gynecology, University of Leipzig, Germany

Requests for reprints: Arnulf Mayer, Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55128 Mainz, Germany. Phone: 49-6131-392-5203; Fax: 49-6131-392-5774; E-mail: arnmayer{at}uni-mainz.de.

Purpose: Glucose transporter-1 (GLUT-1), a target gene of hypoxia-inducible factor-1, has been considered a candidate endogenous marker of tumor hypoxia. Expression of GLUT-1 may also serve as an indicator for the induction of the transcriptional response to hypoxia, which has been linked to enhanced proliferation, resistance to therapy, and metastatic propagation of cancer cells. Overexpression of GLUT-1 has been shown to correlate with poor prognosis in several tumor entities, among them cancers of the uterine cervix. The validity of these hypotheses is investigated.

Experimental Design: The expression of GLUT-1 was assessed in 80 biopsies of Eppendorf oxygenation measurement tracks from locally advanced cervical cancers in 47 patients using immunohistochemistry.

Results: No correlation was found between the expression of GLUT-1 and oxygenation variables (median pO₂, HF 2.5 and HF 5). Expression of GLUT-1 was found greater in larger tumors (P = 0.0001) and to exhibit a linear increase with Fédération Internationale de Gynécologie et d' Obstétrique stage (P = 0.002). Overall survival (P = 0.004) and recurrence-free survival (P = 0.007) were significantly shorter for patients with expression of GLUT-1. In the subgroup of patients treated with surgery, this effect on prognosis was not independent when pT stage or pN stage were included in a multivariate Cox proportional hazards model.

Conclusions: The suitability of GLUT-1 as an endogenous marker of tumor hypoxia seems questionable. The association with prognosis may partially depend on confounding factors.

Key Words: Hypoxia marker • Tumor hypoxia • Prognosis • Oxygen measurements

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