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 Federation Internationale de Gynecologie et d' Obstetrique 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.
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 Federation Internationale de Gynecologie et d' Obstetrique 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.
Authors: Steffi Lehmann; Daniel P Stiehl; Michael Honer; Marco Dominietto; Ruth Keist; Ivana Kotevic; Kristin Wollenick; Simon Ametamey; Roland H Wenger; Markus Rudin Journal: Proc Natl Acad Sci U S A Date: 2009-07-31 Impact factor: 11.205
Authors: Saskia E Rademakers; Paul N Span; Johannes H A M Kaanders; Fred C G J Sweep; Albert J van der Kogel; Johan Bussink Journal: Mol Oncol Date: 2008-03-27 Impact factor: 6.603
Authors: Hedwig P van de Nieuwenhof; Joanne A de Hullu; Johannes H A M Kaanders; Johan Bulten; Leon F A G Massuger; Léon C L T van Kempen Journal: Virchows Arch Date: 2010-10-02 Impact factor: 4.064