title: Expression of cocaine- and amphetamine-regulated transcript is associated with worse survival in small bowel carcinoid tumors.
abstract: OBJECTIVE
  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 carcinoids. The main objective of the present study was to examine whether CART expression is associated with survival in patients with small bowel carcinoid. Secondary aims were to assess whether CART expression is associated with other tumor characteristics or clinical symptoms.
  
  
  METHODS
  Specimens from 97 patients with small bowel carcinoids were examined for CART expression using immunohistochemistry. A CART score was introduced on the basis of the proportion of CART immunoreactive cells. On inclusion, specimens were examined by routine histopathologic methods and detailed clinical patient data were retrieved. The effect of CART on cell viability was assessed in vitro using two intestinal tumor cell lines.
  
  
  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 HR, 5.47; 95% confidence interval (CI), 0.71-42.46; and High CART HR, 9.44; 95% CI, 1.14-78.14]. CART expression was not associated with patient age, disease stage, tumor grade, or any presenting symptom. Supporting our clinical data, we found that CART promoted tumor cell viability in vitro in two different tumor cell lines.
  
  
  CONCLUSIONS
  Expression of CART in small bowel carcinoid tumors is associated with worse survival.
authors.affiliation: Department of Surgery, Ryhov Hospital, Jönköping, Sweden. kalle.landerholm@lj.se
authors.forename: Kalle
authors.initials: K
authors.lastname: Landerholm
authors.forename: Liliya
authors.initials: L
authors.lastname: Shcherbina
authors.forename: Sture E
authors.initials: SE
authors.lastname: Falkmer
authors.forename: Johannes
authors.initials: J
authors.lastname: Järhult
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053208:Kaplan-Meier Estimate; D051379:Mice; D008875:Middle Aged; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein