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

ABSTRACT

The high prevalence of colorectal carcinoma [CRC] is a driver to understand the underlying molecular mechanisms. Chemoprevention strategy using non-steroidal anti- inflammatory 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. beta-Catenin is a component of the WNT [wing1ss type] signaling pathway, increased protein concentrations promote transcription of genes important in regulating the cell cycle. To determine the significance of COX-2 and beta-catenin expression in colorectal carcinogenesis and prognosis. Thirty patients with colorectal carcinomas treated by colonic resection were studied for the expression of both COX-2 and beta-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. Our results showed that in normal adjacent colonic mucosa, COX-2 was completely absent, whereas beta-catenin was specifically located in the plasma membranes. Both proteins were expressed in tumorous tissues, COX-2 showed diffuse cytoplasmic positivity, whereas 3-catenin accumulated in both the cytoplasm and nuclei. We established statistically significant relationships between pathological grade and both beta-catenin, and COX-2 positivity scores, being at the higher end for poorly-differentiated tumors. beta-Catenin expression also correlated significantly with higher tumor stage and LN metastasis. Both COX-2 and beta-catenin expression correlated with a higher incidence of shorter disease free survival