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dc.contributor.authorAirley, R
dc.contributor.authorLoncaster, Juliette A
dc.contributor.authorDavidson, Susan E
dc.contributor.authorBromley, Michael
dc.contributor.authorRoberts, Stephen A
dc.contributor.authorPatterson, Adam V
dc.contributor.authorHunter, Robin D
dc.contributor.authorStratford, Ian J
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2009-11-06T15:14:53Z
dc.date.available2009-11-06T15:14:53Z
dc.date.issued2001-04
dc.identifier.citationGlucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. 2001, 7 (4):928-34 Clin. Cancer Res.en
dc.identifier.issn1078-0432
dc.identifier.pmid11309343
dc.identifier.urihttp://hdl.handle.net/10541/85550
dc.description.abstractHypoxic tumors are known to be more malignant, to be more likely to metastasize, and to have a poor prognosis. They are also radio- and chemoresistant. For this reason, it is desirable that a clinically useful marker of hypoxia is found, so that treatment with radiotherapy and bioreductive chemotherapy can be rationally applied to individual patients. Glut-1 is a facilitative glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intrinsic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phosphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven predictive qualities, is a suitable gold standard used in our laboratory to validate new hypoxia markers. Using this technique, pretreatment pO(2) measurements were performed on 54 patients with locally advanced cervical carcinoma. Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initiation of treatment. By using a low-tech scoring system, pO(2) was found to correlate 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 examined the prognostic significance of Glut-1 staining in a retrospective series of 121 patients. An absence of Glut-1 significantly increased the likelihood of metastasis-free survival (P = 0.022) but did not significantly effect 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 clinical setting.
dc.language.isoenen
dc.subjectBiological Tumour Markersen
dc.subjectUterine Cervical Canceren
dc.subject.meshAnoxia
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshGlucose Transporter Type 1
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshMiddle Aged
dc.subject.meshMonosaccharide Transport Proteins
dc.subject.meshOxygen
dc.subject.meshPrognosis
dc.subject.meshTumor Markers, Biological
dc.subject.meshUterine Cervical Neoplasms
dc.titleGlucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Experimental Radiation Oncology Group, Paterson Institute for Cancer Research.en
dc.identifier.journalClinical Cancer Researchen
html.description.abstractHypoxic tumors are known to be more malignant, to be more likely to metastasize, and to have a poor prognosis. They are also radio- and chemoresistant. For this reason, it is desirable that a clinically useful marker of hypoxia is found, so that treatment with radiotherapy and bioreductive chemotherapy can be rationally applied to individual patients. Glut-1 is a facilitative glucose transporter that is ubiquitously expressed in normal tissue and expressed at higher levels in a number of tumors. Its potential as an intrinsic hypoxia marker arises from its dual control in hypoxic conditions by reduced oxidative phosphorylation and the hypoxia-inducible factor (HIF-1) oxygen-sensing pathway. Eppendorf histography, by virtue of its proven predictive qualities, is a suitable gold standard used in our laboratory to validate new hypoxia markers. Using this technique, pretreatment pO(2) measurements were performed on 54 patients with locally advanced cervical carcinoma. Then, immunohistochemical staining was used to detect Glut-1 protein in individual tumor biopsy sections. Both measurements were made before initiation of treatment. By using a low-tech scoring system, pO(2) was found to correlate 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 examined the prognostic significance of Glut-1 staining in a retrospective series of 121 patients. An absence of Glut-1 significantly increased the likelihood of metastasis-free survival (P = 0.022) but did not significantly effect 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 clinical setting.


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