Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non–Small-Cell Lung Cancer
| العنوان: | Carbonic Anhydrase IX Expression, a Novel Surrogate Marker of Tumor Hypoxia, Is Associated With a Poor Prognosis in Non–Small-Cell Lung Cancer |
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| المؤلفون: | J. Louise Jones, Nick Taub, Daniel E.B. Swinson, Kenneth J. O'Byrne, Helen Turley, Adrian L. Harris, Donna Richardson, Jaromir Pastorek, Charles C. Wykoff |
| المصدر: | Journal of Clinical Oncology. 21:473-482 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Lung Neoplasms, Stromal cell, Survival, Blotting, Western, CA 15-3, Necrosis, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, Tumor Cells, Cultured, medicine, Humans, Carbonic Anhydrase IX, Lung cancer, Aged, Carbonic Anhydrases, Tumor marker, Neovascularization, Pathologic, Tumor hypoxia, business.industry, Middle Aged, Carbonic Anhydrase 9, Prognosis, medicine.disease, Immunohistochemistry, Cell Hypoxia, Tumor antigen, Neoplasm Proteins, Oxygen tension, Isoenzymes, Phenotype, Oncology, Disease Progression, Cancer research, Female, business |
| الوصف: | 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. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6decc191e90857644034e8a80284aa1Test https://doi.org/10.1200/jco.2003.11.132Test |
| رقم الانضمام: | edsair.doi.dedup.....e6decc191e90857644034e8a80284aa1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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