An Evaluation of Cyclooxygenase-2 as a Prognostic Biomarker in Mid-Gut Carcinoid Tumours

Background/Aims: Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC. Methods: Tissue from the primary MGC tumours of 37 patients was subjected to immunohistochemical detection of Cox-2 and Bcl-2. In 9 cases, tissue from secondary lesions was also examined. The study assessed whether tumour-associated Cox-2 and Bcl-2 expression were related to patient survival. Results: Cox-2 expression was demonstrated in 30/36 primary tumours. When all tumours were analysed, Cox regression analysis indicated a trend towards worsening survival with increasing Cox-2 histoscore (intensity × proportion; hazard ratio 1.53, 95% CI 0.93, 2.52; p = 0.09). Analysis of Cox-2-positive tumours revealed a highly significant association between increasing histoscore and decreased survival (hazard ratio 3.03, 95% CI 1.33, 6.91; p = 0.008). Tumour-associated Bcl-2 expression had no effect on patient survival (hazard ratio 1.12, 95% CI 0.42, 2.99; p = 0.82). There was no significant association between Cox-2 and Bcl-2 expression (χ 2 p = 0.16), or Cox-2 histoscore and Bcl-2 expression (MWU p = 0.59). Analysis of the Cox-2 histoscores of primary tumours and their corresponding secondary lesions revealed a statistically significant trend towards increasing histoscore in the latter (Wilcoxon p = 0.04). Conclusions: This study has provided evidence that Cox-2 expression in primary MGC may be associated with a more negative prognostic outlook.