Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782286558524604416 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3790183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT klimowiczac theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT bosep theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT petrillosk theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT maglioccoam theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT dortjc theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT brocktonnt theprognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT klimowiczac prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT bosep prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT petrillosk prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT maglioccoam prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT dortjc prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma AT brocktonnt prognosticimpactofacombinedcarbonicanhydraseixandki67signatureinoralsquamouscellcarcinoma |