Prognostic significance of COX-2 and b-catenin in colorectal carcinoma

Abstract

Background: The high prevalence of colorectal carcinoma (CRC) is a driver to understand the underlying molecular mechanisms. Chemoprevention strategy using non-steroidal antiinflammatory drugs (NSAIDs) revealed that these drugs suppress colorectal carcinoma. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes. The function of prostaglandins and cyclooxygenase in cancer pathogenesis is unclear. COX-2 regulation of proliferation, apoptosis, and tumor-blood vessel interaction has been suggested. b-Catenin is a component of the WNT (wingless type) signaling pathway, increased protein concentrations promote transcription of genes important in regulating the cell cycle.
Aim: To determine the significance of COX-2 and b-catenin expression in colorectal carcinogenesis and prognosis.
Patients and methods: Thirty patients with colorectal carcinomas treated by colonic resection were studied for the expression of both COX-2 and b-catenin by immunohistochemistry. Their expression was interpreted in relation to adjacent normal colonic mucosa and analyzed in correlation with various clinicopathologic parameters and patient’s survival after a follow up period of 24 months.
Results: Our results showed that in normal adjacent colonic mucosa, COX-2 was completely absent, whereas b-catenin was specifically located in the plasma membranes. Both proteins were expressed in tumorous tissues, COX-2 showed diffuse cytoplasmic positivity, whereas b-catenin accumulated in both the cytoplasm and nuclei. We established statistically significant relationships between pathological grade and both b-catenin, and COX-2 positivity scores, being at the higher end for poorly-differentiated tumors. b-Catenin expression also correlated significantly with higher tumor stage and LN metastasis. Both COX-2 and b-catenin expression correlated with a higher incidence of shorter disease free survival.
Conclusion: Both b-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

Keywords: b-Catenin COX-2 Colorectal carcinoma Immunohistochemistry Prognosis