Expression of tachykinins by ileal and lung carcinoid tumors assessed by combined in situ hybridization, immunocytochemistry, and radioimmunoassay.

Abstract

Mid-gut carcinoid tumors have been shown to produce substance P, a tachykinin. A recent addition to this family of peptides is neurokinin A which is cleaved from the same precursor as substance P; beta-pre-pro-tachykinin. The authors have examined mid-gut and pulmonary carcinoid tumors for the presence of the two tachykinins, using immunocytochemical study and radioimmunoassay, and have applied the techniques of in situ hybridization and Northern blot analysis to investigate the expression of mRNA for beta-pre-pro-tachykinin. All gut tumors (n = 8) and three of the six lung tumors examined were found by immunocytochemical study to contain both tachykinins or neurokinin A alone. Chromatographic analysis of tumor extracts suggests that this peptide is being detected as a separate molecule and/or as the C-terminal portion of a larger, uncleaved form. Three of the cases positive for tachykinins showed no detectable serotonin immunoreactivity. Strong hybridization signals for beta-pre-pro-tachykinin mRNA were seen in all but one of the cases studied which contained tachykinin immunoreactivity. Intact mRNA and positive hybridization was found by Northern blot analysis in two mid-gut tumors. Concentrations of tachykinins were found by radioimmunoassay to be higher in mid-gut tumors (substance P 27.2 +/- 19.7 pmol/g; neurokinin A 31.8 +/- 24.2 pmol/g; mean +/- SEM, n = 5) than in lung cases (substance P mean 0.8, range 0.5-1.0 pmol/g; neurokinin A mean 11.0, range 10.0-12.0 pmol/g; n = 3). These results show that mid-gut and pulmonary carcinoid tumors produce tachykinins, which are detected, in some cases, where no serotonin immunoreactivity can be found, possibly because of a high rate of amine secretion. Screening for tachykinins may prove to be a useful diagnostic adjunct for these tumors.