Expression of Cocaine- and Amphetamine-Regulated Transcriptis Associated with Worse Survival in Small Bowel Carcinoid Tumors

• Published in: Clinical cancer research 2012, Vol.18 (13), p.3668
• Main Authors: Landerholm, Kalle, Shcherbina, Liliya, Falkmer, Sture E, Järhult, Johannes, Wierup, Nils
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-11-2513

Purpose: Cocaine- and amphetamine-regulated transcript (CART) peptide exerts several regulatory functions acting both as neurotransmitter and hormone. We recently showed that CART is expressed in various neuroendocrine tumors, including small bowel carcinoid. The main objective of the present study was to examine whether CART expression is associated with survival in small bowel carcinoid patients. Secondary aims were to assess if CART expression is associated with other tumor characteristics or clinical symptoms. Experimental Design: Specimens from 97 patients with small bowel carcinoids were examined for CART expression using immunohistochemistry and in situ hybridization. A CART score was introduced based on the proportion of CART immunoreactive cells. On inclusion, specimens were examined by routine histopathological methods and detailed clinical patient data were retrieved. The effect of CART on cell viability was assessed in vitro using an enteroendocrine cell line. Results: Expression of CART (P = 0.011), and increasing CART score ( P = 0.033) were associated with worse disease-specific survival. Adjusting for age, disease stage and tumor grade in multivariable analysis, CART expression was still associated with worse survival ( Low CART hazard ratio (HR) 5.47, 95% confidence interval (CI) 0.71 to 42.46; and High CART HR 9.44, 95% CI 1.14 to 78.14). Expression of CART correlated with higher tumor grade, but not with age or disease stage, neither with weight loss or any other symptom. Supporting our clinical data, we found that CART promoted tumor cell viability in vitro . Conclusion: Expression of CART in small bowel carcinoid tumors is associated with worse survival.