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The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma

BACKGROUND: Tumour hypoxia is associated with impaired apoptosis, resistance to therapy and poor prognosis. We previously reported that high stromal expression of the endogenous marker of hypoxia, carbonic anhydrase IX (CAIX), is associated with significantly reduced survival in oral squamous cell c...

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Autores principales: Klimowicz, A C, Bose, P, Petrillo, S K, Magliocco, A M, Dort, J C, Brockton, N T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790183/
https://www.ncbi.nlm.nih.gov/pubmed/24008660
http://dx.doi.org/10.1038/bjc.2013.533
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author Klimowicz, A C
Bose, P
Petrillo, S K
Magliocco, A M
Dort, J C
Brockton, N T
author_facet Klimowicz, A C
Bose, P
Petrillo, S K
Magliocco, A M
Dort, J C
Brockton, N T
author_sort Klimowicz, A C
collection PubMed
description BACKGROUND: Tumour hypoxia is associated with impaired apoptosis, resistance to therapy and poor prognosis. We previously reported that high stromal expression of the endogenous marker of hypoxia, carbonic anhydrase IX (CAIX), is associated with significantly reduced survival in oral squamous cell carcinoma (OSCC). In addition to hypoxia, CAIX expression is regulated by proliferation-associated signalling. We hypothesised that incorporating Ki67, a proliferation marker, into our existing CAIX-based stratification of OSCC would identify patients with the least favourable prognosis. METHODS: Surgically resected tumours from 60 OSCC patients were analysed for CAIX, Ki67 and BAX expression using fluorescence immunohistochemistry and automated quantitative analysis (AQUA). RESULTS: In patients expressing high stromal CAIX (sCAIX), stratification by tumour Ki67 expression revealed significantly distinct survival outcomes (P=0.005). In our OSCC cohort, below-median Ki67 and top-quartile sCAIX expression (Ki67(lo)sCAIX(hi)) were associated with significantly worse disease-specific survival in univariate (HR 7.2 (2.5–20.4), P=0.001) and multivariate (HR 4.2 (1.4–12.8), P=0.011) analyses. Hypoxia is associated with decreased BAX expression; the Ki67(lo)sCAIX(hi) group was more strongly associated with low BAX expression than high sCAIX alone. CONCLUSION: These data suggest that combined analysis of tumour Ki67 and sCAIX expression may provide a more clinically relevant assessment of tumour hypoxia in OSCC.
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spelling pubmed-37901832013-10-21 The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma Klimowicz, A C Bose, P Petrillo, S K Magliocco, A M Dort, J C Brockton, N T Br J Cancer Molecular Diagnostics BACKGROUND: Tumour hypoxia is associated with impaired apoptosis, resistance to therapy and poor prognosis. We previously reported that high stromal expression of the endogenous marker of hypoxia, carbonic anhydrase IX (CAIX), is associated with significantly reduced survival in oral squamous cell carcinoma (OSCC). In addition to hypoxia, CAIX expression is regulated by proliferation-associated signalling. We hypothesised that incorporating Ki67, a proliferation marker, into our existing CAIX-based stratification of OSCC would identify patients with the least favourable prognosis. METHODS: Surgically resected tumours from 60 OSCC patients were analysed for CAIX, Ki67 and BAX expression using fluorescence immunohistochemistry and automated quantitative analysis (AQUA). RESULTS: In patients expressing high stromal CAIX (sCAIX), stratification by tumour Ki67 expression revealed significantly distinct survival outcomes (P=0.005). In our OSCC cohort, below-median Ki67 and top-quartile sCAIX expression (Ki67(lo)sCAIX(hi)) were associated with significantly worse disease-specific survival in univariate (HR 7.2 (2.5–20.4), P=0.001) and multivariate (HR 4.2 (1.4–12.8), P=0.011) analyses. Hypoxia is associated with decreased BAX expression; the Ki67(lo)sCAIX(hi) group was more strongly associated with low BAX expression than high sCAIX alone. CONCLUSION: These data suggest that combined analysis of tumour Ki67 and sCAIX expression may provide a more clinically relevant assessment of tumour hypoxia in OSCC. Nature Publishing Group 2013-10-01 2013-09-05 /pmc/articles/PMC3790183/ /pubmed/24008660 http://dx.doi.org/10.1038/bjc.2013.533 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Klimowicz, A C
Bose, P
Petrillo, S K
Magliocco, A M
Dort, J C
Brockton, N T
The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title_full The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title_fullStr The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title_full_unstemmed The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title_short The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma
title_sort prognostic impact of a combined carbonic anhydrase ix and ki67 signature in oral squamous cell carcinoma
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790183/
https://www.ncbi.nlm.nih.gov/pubmed/24008660
http://dx.doi.org/10.1038/bjc.2013.533
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