Expression of Beta-catenin, COX-2 and iNOS in Colorectal Cancer: Relevance of COX-2 and iNOS Inhibitors for Treatment in Malaysia

• Main Authors: Seok Kwan Hong, Hairuszah Ithnin, Heng Fong Seow
• Format: Article
• Language: English
• Published: Elsevier 2004-01-01
• Series: Asian Journal of Surgery
• Online Access: http://www.sciencedirect.com/science/article/pii/S1015958409602372

Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression of β-catenin and the presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 and iNOS. Methods: A cross-sectional study using retrospective data over a 2-year period (1999–2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral centre. Results: COX-2 production was detected in adjacent normal tissue in 34 samples (33.7 %) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense β-catenin immunoreactivity was found in both the cytoplasm and nuclei of tumour cells, with a distinct loss of β-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total β-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and β-catenin, COX-2 and iNOS scores. Conclusions: The accumulation of β-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.