Tachykinins in endocrine tumors and the carcinoid syndrome.
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).


METHODS
TK, serotonin and chromogranin A (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 out 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-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA 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.


CONCLUSIONS
We found that TK synthesis occurs in serotonin-IR tumors and that P-TK levels are significantly correlated with 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.
Departments of Medical Sciences Genetics and Pathology, University Hospital, SE 751 85 Uppsala, Sweden. janet.cunningham@medsci.uu.se
Janet L
JL
Cunningham
Eva T
ET
Janson
Smriti
S
Agarwal
Lars
L
Grimelius
Mats
M
Stridsberg
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000378:metabolism; D004701:Endocrine Gland Neoplasms / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008303:Malignant Carcinoid Syndrome / Q000097:blood / Q000378:metabolism*; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D017385:Sequence Homology; D015320:Tachykinins / Q000097:blood / Q000276:immunology / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015320:Tachykinins