Microregional expression of glucose transporter-1 and oxygenation status: lack of correlation in locally advanced cervical cancers.
OBJECTIVE
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.


METHODS
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.
Mayer
Arnulf
A
Institute of Physiology and Pathophysiology, University of Mainz, Germany. arnmayer@uni-mainz.de
Höckel
Michael
M
Wree
Alexander
A
Vaupel
Peter
P
D005260:Female; D051272:Glucose Transporter Type 1; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000706:statistics & numerical data; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010100:Oxygen / Q000378:metabolism*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D010100:Oxygen