Expression and association of carbonic anhydrase IX and cyclooxygenase-2 in colorectal cancer

Pathol Res Pract. 2019 Apr;215(4):705-711. doi: 10.1016/j.prp.2019.01.012. Epub 2019 Jan 7.

Abstract

Background: This work was designed to determine the relationship between hypoxia-inducible protein carbonic anhydrase IX (CA IX) and pro-inflammatory enzyme cyclooxygenase-2 (COX-2) in patients with colorectal cancer (CRC).

Methods: We examined CA IX and COX-2 expression in CRC tissues by immunohistochemical staining of 111 samples. We evaluated the correlation between the expression of these proteins and their correlation with the clinico-morphological parameters of CRC.

Results: CA IX was detected in 89 of 111 cases (80.2%). We predominantly observed membrane staining (70.3%) and a strong immunoreaction intensity (58.6%). The percentage of labeled cells in malignant lesions was less than 25% in 12.6% of cases, less than 50% in 15.3% of cases and more than 50% in 52.3% of CRC cases. The COX-2 protein was expressed in 94 of 111 cases (84.7%). We noticed only cytoplasmic localization, while immunoreaction intensity was predominantly strong (47.8%). The percentage of COX-2 positive cells was less than 25% only in 2.7% of the cases, less than 50% in 21.6% of the cases and more than 50% in 60.4% of the cases. No statistically significant correlations were observed between CA IX expression and clinico-morphological parameters. COX-2 expression was only significantly correlated with the tumor stage. Statistical analysis confirmed a significant correlation between the parameters of expression of the CA IX and COX-2 proteins.

Conclusion: CA IX/COX-2 interplay can promote hypoxia survival and the invasion of tumor cells. These proteins may represent independent prognostic factors of CRC.

Keywords: Carbonic anhydrase IX; Colorectal cancer; Cyclooxygenase-2; Hypoxia; Immunohistochemistry; Inflammation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carbonic Anhydrase IX / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Cyclooxygenase 2
  • Carbonic Anhydrase IX