An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours.
OBJECTIVE
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 x 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 (chi(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.
Cadden
Ian
I
Department of Medicine, Queen's University Belfast, Mulhouse Building, RGH, Belfast, Northern Ireland, UK.
Johnston
Brian T
BT
Turner
Graham
G
McCance
David
D
Ardill
Joy
J
McGinty
Ann
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001065:Appendix / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D003106:Colon / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2