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dc.contributor.authorHutchison, Gillian J
dc.contributor.authorValentine, Helen R
dc.contributor.authorLoncaster, Juliette A
dc.contributor.authorDavidson, Susan E
dc.contributor.authorHunter, Robin D
dc.contributor.authorRoberts, Stephen A
dc.contributor.authorHarris, Adrian L
dc.contributor.authorStratford, Ian J
dc.contributor.authorPrice, Patricia M
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2009-08-20T12:10:38Z
dc.date.available2009-08-20T12:10:38Z
dc.date.issued2004-12-15
dc.identifier.citationHypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. 2004, 10 (24):8405-12 Clin. Cancer Res.en
dc.identifier.issn1078-0432
dc.identifier.pmid15623619
dc.identifier.doi10.1158/1078-0432.CCR-03-0135
dc.identifier.urihttp://hdl.handle.net/10541/78011
dc.description.abstractPURPOSE: Hypoxia-inducible factor (HIF)-1alpha expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy. EXPERIMENTAL DESIGN: HIF-1alpha expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9. RESULTS: High HIF-1alpha expression showed a weak correlation with low pO2 (r = -0.26; P = 0.030; n = 72). Weak significant correlations were found between HIF-1alpha and pimonidazole staining (r = 0.34; P = 0.040; n = 36) and carbonic anhydrase IX (r = 0.27; P = 0.001; n = 160). There was no relationship with surviving fraction at 2 Gy. The relationship between HIF-1alpha expression and radiotherapy outcome was examined in 99 patients. HIF-1alpha expression did not correlate with disease stage, grade, tumor size, and patient age. HIF-1alpha alone was not a significant prognostic factor for disease-free survival, metastasis-free survival, or local recurrence-free survival. High HIF-1alpha expression tended to be associated with poor outcome in small tumors but good outcome in large tumors, with statistically significant interactions between HIF-1alpha and tumor size for survival (P = 0.046) and local control (P = 0.009). CONCLUSIONS: In this study, HIF-1alpha had no prognostic significance in locally advanced carcinoma of the cervix. The possible switch in large tumors for an association between high HIF-1alpha expression and good outcome might relate to tumor size-related changes in the balance of genes up-regulated by HIF-1alpha. Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. This hypothesis needs testing in future work.
dc.language.isoenen
dc.subjectCancer Recurrenceen
dc.subjectTumour Markersen
dc.subjectUterine Cervical Canceren
dc.subject.meshAnoxia
dc.subject.meshAntigens, Neoplasm
dc.subject.meshCarbonic Anhydrases
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit
dc.subject.meshIon-Selective Electrodes
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Recurrence, Local
dc.subject.meshNitroimidazoles
dc.subject.meshOxygen
dc.subject.meshPrognosis
dc.subject.meshRadiation-Sensitizing Agents
dc.subject.meshSurvival Rate
dc.subject.meshTranscription Factors
dc.subject.meshTreatment Outcome
dc.subject.meshTumor Markers, Biological
dc.subject.meshUterine Cervical Neoplasms
dc.titleHypoxia-inducible factor 1alpha expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix.en
dc.typeArticleen
dc.contributor.departmentAcademic Department of Radiation Oncology, The University of Manchester, Christie Hospital NHS Trust, Manchester, United Kingdom.en
dc.identifier.journalClinical Cancer Researchen
html.description.abstractPURPOSE: Hypoxia-inducible factor (HIF)-1alpha expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy. EXPERIMENTAL DESIGN: HIF-1alpha expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9. RESULTS: High HIF-1alpha expression showed a weak correlation with low pO2 (r = -0.26; P = 0.030; n = 72). Weak significant correlations were found between HIF-1alpha and pimonidazole staining (r = 0.34; P = 0.040; n = 36) and carbonic anhydrase IX (r = 0.27; P = 0.001; n = 160). There was no relationship with surviving fraction at 2 Gy. The relationship between HIF-1alpha expression and radiotherapy outcome was examined in 99 patients. HIF-1alpha expression did not correlate with disease stage, grade, tumor size, and patient age. HIF-1alpha alone was not a significant prognostic factor for disease-free survival, metastasis-free survival, or local recurrence-free survival. High HIF-1alpha expression tended to be associated with poor outcome in small tumors but good outcome in large tumors, with statistically significant interactions between HIF-1alpha and tumor size for survival (P = 0.046) and local control (P = 0.009). CONCLUSIONS: In this study, HIF-1alpha had no prognostic significance in locally advanced carcinoma of the cervix. The possible switch in large tumors for an association between high HIF-1alpha expression and good outcome might relate to tumor size-related changes in the balance of genes up-regulated by HIF-1alpha. Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. This hypothesis needs testing in future work.


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