Polish Journal of Pathology
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ISSN: 1233-9687
Polish Journal of Pathology
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vol. 76
 
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Original paper

Immunohistochemical expression and association of hypoxia-inducible factor 1a and carbonic anhydrase IX in colorectal cancer

Veronika Cígerová
1
,
Marian Adamkov
1
,
Marián Grendár
2
,
Veronika Mešťanová
1

  1. Department of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
  2. Department of Bioinformatics, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
Pol J Pathol 2025; 76 (1): 16-24
Online publish date: 2025/05/10
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1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-249.
2. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 2009; 361: 2449-2460.
3. Zou YF, Rong YM, Tan YX, et al. A signature of hypoxia-related factors reveals functional dysregulation and robustly predicts clinical outcomes in stage I/II colorectal cancer patients. Cancer Cell Int 2019; 19: 243.
4. Momin S, Nagaraju GP. The role of hypoxia-inducible factor 1-alpha in colorectal cancer. In: Theranostics approaches to gastric and colon cancer. Springer 2020, 61-68.
5. Masoud GN, Li W. HIF-1a pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B 2015; 5: 378-389.
6. Chen Y, Li X, Wu S, et al. Expression of HIF-1a and CAIX in nasopharyngeal carcinoma and their correlation with patients’ prognosis. Med Oncol 2014; 31: 304.
7. Courtnay R, Ngo DC, Malik N, et al. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep 2015; 42: 841-851.
8. Pastorekova S, Ratcliffe PJ, Pastorek J. Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia. BJU Int 2008; 101: 8-15.
9. Sedlakova O, Svastova E, Takacova M, et al. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors. Front Physiol 2014; 4: 1-14.
10. Wigerup C, Påhlman S, Bexell D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol Ther 2016; 164: 152-169.
11. Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer 2011; 11: 393-410.
12. Pastorek J, Pastorekova S. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use. Semin Cancer Biol 2015; 31: 52-64.
13. McDonald PC, Winum J-W, Supuran CT, et al. Recent developments in targeting carbonic anhydrase IX for cancer therapeutics. Oncotarget 2012; 3: 84-97.
14. Lee S-H, Griffiths JR. How and why are cancers acidic? Carbonic anhydrase IX and the homeostatic control of tumour extracellular pH. Cancers 2020; 12: 1616.
15. Korkeila E, Talvinen K, Jaakkola PM, et al. Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer. Br J Cancer 2009; 100: 874-880.
16. Viikilä P, Kivelä AJ, Mustonen H, et al. Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas. World J Gastroenterol 2016; 22: 8168-8177.
17. Kalinin S, Malkova A, Sharonova T, et al. Carbonic anhydrase IX inhibitors as candidates for combination therapy of solid tumors. Int J Mol Sci 2021; 22: 13405.
18. Goethals L, Debucquoy A, Perneel C, et al. Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers. Int J Radiat Oncol Biol Phys 2006; 65: 246-254.
19. Cleven AH, van Engeland M, Wouters BG, et al. Stromal expression of hypoxia regulated proteins is an adverse prognostic factor in colorectal carcinomas. Cell Oncol 2007; 29: 229-240.
20. Saka B, Ekinci O, Dursun A, et al. Clinicopathologic and prognostic significance of immunohistochemical expression of HIF-1a, CXCR4 and CA9 in colorectal carcinoma. Pathol Res Pract 2017; 213: 783-792.
21. Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system (4th ed.). Lyon: IARC Press 2010, 417.
22. Kuan SF, Navina S, Cressman KL, et al. Immunohistochemical detection of BRAF V600E mutant protein using the VE1 antibody in colorectal carcinoma is highly concordant with molecular testing but requires rigorous antibody optimization. Human Pathol 2014; 45: 464-472.
23. R Core Team (2021) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria 2021. Available from: https://www.R-project.org/ (accessed: 6.11.2022).
24. Takácová M, Pastoreková S. Tumour hypoxia – molecular mechanisms and clinical relevance. Klin Onkol 2015; 28: 183-190.
25. Greijer AE, Delis-Van Diemen PM, Fijneman RJ, et al. Presence of HIF-1 and related genes in normal mucosa, adenomas and carcinomas of the colorectum. Virch Arch 2008; 452: 535-544.
26. Furlan D, Sahnane N, Carnevali I, et al. Up-regulation and stabilization of HIF-1alpha in colorectal carcinomas. Surg Oncol 2007; 6: 25-27.
27. Yoshimura H, Dhar DK, Kohno H, et al. Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression. Clin Cancer Res 2004; 10: 8554-8560.
28. Fan LF, Dong WG, Jiang CQ, et al. Role of hypoxia-inducible factor-1a and survivin in colorectal carcinoma progression. Int J Colorectal Dis 2008; 23: 1057-1064.
29. Wu Y, Jin M, Xu H, et al. Clinicopathologic significance of HIF-1a, CXCR4, and VEGF expression in colon cancer. Clin Dev Immunol 2010; 2010: 537531.
30. Saarnio J, Parkkila S, Parkkila AK, et al. Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. Am J Pathol 1998; 153: 279-285.
31. Hong YS, Cho HJ, Kim SY, et al. Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer. BMC Cancer 2009; 9: 1-9.
32. Rasheed S, Harris AL, Tekkis PP, et al. Assessment of microvessel density and carbonic anhydrase-9 (CA-9) expression in rectal cancer. Pathol Res Pract 2009; 205: 1-9.
33. Kovácová Z, Hodorová I. Carbonic anhydrase IX and survivin in colorectal adenocarcinoma cells: Slovakian population study. Biology 2021; 10: 872.
34. Vleugel MM, Greijer AE, Shvarts A, et al. Differential prognostic impact of hypoxia induced and diffuse HIF-1alpha expression in invasive breast cancer. J Clin Pathol 2005; 58: 172-177.
35. Iwasaki K, Yabushita H, Ueno T, et al. Role of hypoxia-inducible factor-1a, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer. Oncol Lett 2015; 10: 1970-1978.
36. Sobhanifar S, Aquino-Parsons C, Stanbridge EJ, et al. Reduced expression of hypoxia-inducible factor-1 alpha in perinecrotic regions of solid tumors. Cancer Res 2005; 65: 7259-7266.
37. Kaluz S, Kaluzova M, Liao SY, et al. Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show? Biochim Biophys Acta 2009; 1795: 162-172.
38. Baba Y, Nosho K, Shima K, et al. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol 2010; 176: 2292-2301.
39. Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011; 10: 767-777.
40. Lock FE, McDonald PC, Lou Y, et al. Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche. Oncogene 2013; 32: 5210-5219.
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