INSITU ANALYSIS OF CALCITONIN AND CGRP EXPRESSION IN MEDULLARY-THYROID CARCINOMA

A combination of immunocytochemistry (ICC) and in‐situ hybridization (ISH) applied to formalin‐fixed tissue sections was used to analyse the differential expression of calcitonin and CGRP genes, at both peptide and mRNA levels, in normal and neoplastic human thyroid C cells. Calcitonin peptide was readily detectable in normal C cells but its abundance in the neoplastic C cells of medullary thyroid carcinoma (MTC) was reduced in correlation with the degree of tumour differentiation. Conversely, the content of calcitonin mRNA was higher in MTC than in normal C cells and was not significantly related to tumour differentiation. Both the peptide and mRNA of CGRP were present at much lower levels than those of calcitonin in normal C cells but were increased in neoplastic C cells. We conclude that neoplasia of thyroid C cells is associated with (i) an increase in the content of CGRP mRNA and peptide relative to that of calcitonin, consistent with a defect in control of transcript processing, and (ii) a decrease in the ratio of calcitonin peptide to mRNA abundance relative to the normal, suggesting a defect in synthesis or storage of the peptide. ISH analysis of calcitonin mRNA may therefore be a very valuable addition to ICC analysis of the peptide as a diagnostic and prognostic marker for MTC. Copyright © 1990, Wiley Blackwell. All rights reserved