Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non–Small-Cell Lung Cancer
Copyright policy )Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non–Small-Cell Lung Cancer
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 CA IX 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.
- University Hospitals of Leicester NHS Trust United Kingdom
- Queensland University of Technology Australia
- Slovak Academy of Sciences Slovakia
Male, oxygen tension, Lung Neoplasms, lung tumor, necrosis, Western blotting, Carcinoma, Non-Small-Cell Lung, middle aged, genetics, carbonate dehydratase IX, Non-Small-Cell Lung, cellular distribution, Carbonic Anhydrases, Neovascularization, Pathologic, Blotting, adult, lung non small cell cancer, disease course, article, cell hypoxia, Middle Aged, Immunohistochemistry, Cell Hypoxia, Neoplasm Proteins, Isoenzymes, aged, female, priority journal, immunohistochemistry, histopathology, Disease Progression, CA9 protein, carbonate dehydratase, Female, isoenzyme, Western, Adult, phenotype, Blotting, Western, protein localization, thrombocyte count, tumor necrosis, survival, Necrosis, tumor protein, male, Antigens, Neoplasm, Biomarkers, Tumor, Humans, controlled study, human, Antigens, Carbonic Anhydrase IX, Aged, cell culture, cancer staging, human cell, Carcinoma, neovascularization (pathology), major clinical study, human tissue, tumor marker, Neoplasm, antigen expression, pathology, prognosis, biosynthesis, tumor antigen
Male, oxygen tension, Lung Neoplasms, lung tumor, necrosis, Western blotting, Carcinoma, Non-Small-Cell Lung, middle aged, genetics, carbonate dehydratase IX, Non-Small-Cell Lung, cellular distribution, Carbonic Anhydrases, Neovascularization, Pathologic, Blotting, adult, lung non small cell cancer, disease course, article, cell hypoxia, Middle Aged, Immunohistochemistry, Cell Hypoxia, Neoplasm Proteins, Isoenzymes, aged, female, priority journal, immunohistochemistry, histopathology, Disease Progression, CA9 protein, carbonate dehydratase, Female, isoenzyme, Western, Adult, phenotype, Blotting, Western, protein localization, thrombocyte count, tumor necrosis, survival, Necrosis, tumor protein, male, Antigens, Neoplasm, Biomarkers, Tumor, Humans, controlled study, human, Antigens, Carbonic Anhydrase IX, Aged, cell culture, cancer staging, human cell, Carcinoma, neovascularization (pathology), major clinical study, human tissue, tumor marker, Neoplasm, antigen expression, pathology, prognosis, biosynthesis, tumor antigen
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).262 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!