Elevated Serum Levels of Calcitonin Gene‐related Peptide (Cgrp) but No Evidence for CGRP Gene Expression in Non‐small Cell Lung Carcinomas

Abstract

Calcitonin gene-related peptide (CGRP) is a hormone formed by alternative post-transcriptional processing of the calcitonin gene. It is a neuropeptide localized to discrete regions of the central nervous system (CNS) and in nerve fibres associated with blood vessels. It is also expressed in medullary carcinomas of the thyroid and lung carcinoma cell lines. The latter finding suggests a possible value for CGRP as tumour marker in lung carcinomas. In this investigation of 22 patients undergoing operation for lung tumours, pre and post-operative levels of serum CGRP were measured. Preoperative as well as postoperative serum CGRP levels were significantly elevated when compared to age-matched normals. However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocytochemistry or in-situ hybridization using CGRP cRNA probes. CGRP has been localized to nerve fibres in relation to pulmonary blood vessels and has been shown to be a potent vasodilator. These findings, and the absence of evidence for synthesis in tumours, as opposed to cell lines derived from lung carcinomas, suggests that the lack of post-operative normalization of serum CGRP concentrations may be related to physiological changes in cardiovascular haemodynamics following surgery. Elevated pre-operative serum CGRP levels may also reflect a consequence of the lung carcinoma leading to increased release of CGRP from sites in the vasculature yet to be determined, but does not indicate synthesis de novo and secretion of CGRP by the tumours.

Calcitonin gene‐related peptide in small cell lung carcinomas

“…Previous investigations have shown that certain lung carcinoma cell-lines may express CGRP Riley et al, 1986) and Riley et al also found increased circulating CGRP-concentrations in lung carcinoma patients. In a previous paper we have demonstrated that CGRP concentrations are significantly elevated in patients with non-SCLC, but this elevation also seemed to be unrelated to synthesis by the tumours since in-situ hybridization and immunohistochemistry showed negative reactions in all the tumours investigated (Schifter et al, 1989). Expression of CGRP has also been demonstrated in other neuroendocrine tumours, including phaeochromocytomas and carcinoid tumours (Johannsen et al, 1987;Funa, 1991).…”

“…In-situ hybridization for CGRP mRNA was performed on 17 tumours. The investigation was performed as described previously (Schifter et al, 1989) using a CGRP cRNA probe derived from a fragment of the calcitonin/cc-CGRP gene, containing exon 6 of the gene. The probe is specific for a-CGRP mRNA under the washing conditions employed.…”

“…We have recently found increased plasma CGRP levels in patients with different types of non-small cell carcinomas of the lung (Schifter et al, 1989), and in a preliminary study increased levels of CGRP were present in 1 1 of 12 patients with untreated small cell lung carcinomas (SCLC) .…”