Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer

Swinson, Daniel E. B., Jones, J. Louise, Richardson, Donna, Wykoff, Charles, Turley, Helen, Pastorek, Jaromir, Taub, Nick, Harris, Adrian L., & O'Byrne, Kenneth J. (2003) Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. Journal of Clinical Oncology, 21(3), pp. 473-482.

View at publisher


Purpose To evaluate carbonic anhydrase (CA) IX as a surrogate marker of hypoxia and investigate the prognostic significance of different patterns of expression in non-small-cell lung cancer (NSCLC).

Methods Standard immunohistochemical techniques were used to study CA IX expression in 175 resected NSCLC tumors. CA IX expression was determined by Western blotting in A549 cell lines grown under normoxic and hypoxic conditions. Measurements from microvessels to CA IX positivity were obtained.

Results CA IX immunostaining was detected in 81.8% of patients. Membranous (m) (P = .005), cytoplasmic (c) (P = .018), and stromal (P < .001) CA IX expression correlated with the extent of tumor necrosis (TN). The mean distance from vascular endothelium to the start of tumor cell positivity was 90 μm, which equates to an oxygen pressure of 5.77 mmHg. The distance to blood vessels from individual tumor cells or tumor cell clusters was greater if they expressed mCA IX than if they did not (P < .001). Hypoxic exposure of A549 cells for 16 hours enhanced CAIX expression in the nuclear and cytosolic extracts. Perinuclear (p) CA IX (P = .035) was associated with a poor prognosis. In multivariate analysis, pCA IX (P = .004), stage (P = .001), platelet count (P = .011), sex (P = .027), and TN (P = .035) were independent poor prognostic factors.

Conclusion These results add weight to the contention that mCA IX is a marker of tumor cell hypoxia. The absence of CA IX staining close to microvessels suggests that these vessels are functionally active. pCA IX expression is representative of an aggressive phenotype. © 2003 by American Society of Clinical Oncology.

Impact and interest:

193 citations in Scopus
184 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 65722
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: carbonate dehydratase IX, CA9 protein, human, carbonate dehydratase, isoenzyme, tumor antigen, tumor marker, tumor protein, adult, aged, antigen expression, article, cancer staging, cell hypoxia, cellular distribution, controlled study, female, histopathology, human, human cell, human tissue, immunohistochemistry, lung non small cell cancer, major clinical study, male, oxygen tension, phenotype, priority journal, prognosis, protein localization, thrombocyte count, tumor necrosis, biosynthesis, cell culture, disease course, genetics, lung tumor, middle aged, necrosis, neovascularization (pathology), pathology, survival, Western blotting, Antigens, Neoplasm, Blotting, Western, Carbonic Anhydrases, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, Isoenzymes, Lung Neoplasms, Neoplasm Proteins, Neovascularization, Pathologic, Tumor Cells, Cultured, Tumor Markers, Biological
DOI: 10.1200/JCO.2003.11.132
ISSN: 0732-183X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2003 American Society of Clinical Oncology
Deposited On: 07 Jan 2014 07:13
Last Modified: 07 Jan 2014 07:16

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page