Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84144
Title:
Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.
Authors:
Loncaster, Juliette A; Harris, Adrian L; Davidson, Susan E; Logue, John P; Hunter, Robin D; Wycoff, C C; Pastorek, J; Ratcliffe, P J; Stratford, Ian J; West, Catharine M L
Abstract:
There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.
Affiliation:
CRC Experimental Radiation Oncology Group, Paterson Institute, Manchester M20 4BX, United Kingdom.
Citation:
Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. 2001, 61 (17):6394-9 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Sep-2001
URI:
http://hdl.handle.net/10541/84144
PubMed ID:
11522632
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLoncaster, Juliette Aen
dc.contributor.authorHarris, Adrian Len
dc.contributor.authorDavidson, Susan Een
dc.contributor.authorLogue, John Pen
dc.contributor.authorHunter, Robin Den
dc.contributor.authorWycoff, C Cen
dc.contributor.authorPastorek, Jen
dc.contributor.authorRatcliffe, P Jen
dc.contributor.authorStratford, Ian Jen
dc.contributor.authorWest, Catharine M Len
dc.date.accessioned2009-10-13T09:22:45Z-
dc.date.available2009-10-13T09:22:45Z-
dc.date.issued2001-09-01-
dc.identifier.citationCarbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. 2001, 61 (17):6394-9 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid11522632-
dc.identifier.urihttp://hdl.handle.net/10541/84144-
dc.description.abstractThere is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.en
dc.language.isoenen
dc.subjectCancer Antigensen
dc.subjectCancer Proteinsen
dc.subjectBiological Tumour Markersen
dc.subjectUterine Cervical Canceren
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshCarbonic Anhydrases-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCell Hypoxia-
dc.subject.meshElectrodes-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMiddle Aged-
dc.subject.meshMultivariate Analysis-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshOxygen-
dc.subject.meshPrognosis-
dc.subject.meshProspective Studies-
dc.subject.meshReproducibility of Results-
dc.subject.meshRetrospective Studies-
dc.subject.meshTreatment Outcome-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleCarbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.en
dc.typeArticleen
dc.contributor.departmentCRC Experimental Radiation Oncology Group, Paterson Institute, Manchester M20 4BX, United Kingdom.en
dc.identifier.journalCancer Researchen

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