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Tachykinins in Endocrine Tumors and the Carcinoid Syndrome

J Cunningham, Medical Sciences, Uppsala University, Uppsala, 75185, Sweden
E Janson, University Hospital, Dept of Medical Science, Uppsala, Sweden
M Stridsberg, Medical Sciences, Uppsala University, Uppsala, Sweden
L Grimelius, Medical Sciences, Uppsala University, Uppsala, Sweden
S Agarwal, Medical Sciences, Uppsala University, Uppsala, Sweden

Correspondence: Janet Cunningham, Email: janet.cunningham{at}medsci.uu.se

Abstract

Objective: A new antibody, active against the common Tachykinin (TK) C-terminal, was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs).

Method: TK, serotonin and chromogranin (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK), and urinary 5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 of the 42 patients.

Results: All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotonin-producing lung and appendix carcinoids. None of the other tumors examined contained TK-immunoreactive cells. P-TK, P-CgA and U-5HIAA concentrations were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms. In a Spearman partial rank test, the correlation of P-TK with daily diarrhea was independent of both U-5HIAA and CgA levels.

Conclusion: We found that TK synthesis occurs in serotonin immunoreactive tumors and that P-TK levels are significantly correlated to symptoms of flush and diarrhea in patients with MSPCs. This is, to our knowledge, the first report demonstrating an independent correlation of P-TKs with carcinoid diarrhea, a symptom that is customarily regarded as serotonin mediated. Further investigations may present opportunities for new therapeutic possibilities.