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The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro‐endocrine bronchial tumours in man
Author(s) -
Vieau D.,
RojasMiranda' A.,
Verley' J. M.,
Lenne F.,
Bertagna And X.
Publication year - 1991
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1991.tb03543.x
Subject(s) - endocrine system , enteroendocrine cell , gastrin releasing peptide , endocrinology , biology , medicine , gastrin , carcinoid tumour , pathology , secretion , neuropeptide , bombesin , hormone , receptor
Summary. O bjective Bronchial tumours are the most frequent cause of the ectopic ACTH syndrome. Two types of tumours are classically responsible: the relatively benign carcinoids and the highly aggressive small cell carcinomas. Both have neuro‐endocrine features and are thought to originate from the endocrine component of the bronchial tree. Our objective was to assess the sensitivity of 7B2 and secretogranin 1 as new biochemical markers of neuro‐endocrine differentiation in these tumours In comparison with gastrin releasing peptide. M ethods Tissue concentration of 7B2, secretogranin 1 fragments (GAWK and CCB), gastrin releasing peptide and 8‐endorphin were measured in normal human lung (n=4), bronchial carcinoid tumours with (n=5) and with‐out (n=15) the ectopic ACTH syndrome, small cell carcinomas (n=2), squamous cell carcinomas (n=11) and adenocarcinomas (n=6). Molecular weight forms of Immunoreactive ‐ACTH, ‐GAWK, ‐gastrin releasing peptide, and ‐7B2 were also examined using gel exclusion chromatography and Western blot analysis. R esults We detected 7B2 immunoreactivity in 19 of 22 neuro‐endocrine lung tumours (with values ranging from <5 to 555 fmol/mg wet weight tissue), CCB immunoreactivity in 20 of 22 tumours with neuro‐endocrine features (with values ranging from <5 to 19 875 fmol mg wet weight tissue) and gastrin releasing peptide immunoreactivity In 10 of 22 neuro‐endocrine lung tumors (with values ranging from <5 to 11132 fmol/mg wet weight tissue). Immunoreactive 7B2 and CCB were detected neither In tumours with non‐endocrine features, nor in the four normal lung specimens. Differing molecular weight forms of Immuno‐reactive 7B2 in two bronchial carcinoids associated with the ectopic ACTH syndrome showed a predominant signal corresponding to a molecular weight of 22 kDa; in addition, a second signal of 19 kDa was also present. The differing molecular weight forms of Immunoreactive ACTH related peptides In the five tumours responsible for the ectopic ACTH syndrome showed, in addition to ACTH 1 ‐ 35 , the constant presence In variable proportions of corticotrophin‐like Intermediary lobe peptide (or ACTH 15 ‐ 39 ). The differing molecular weight forms of Immunoreactive GAWK showed heterogeneous results with materials eluting at Kav of 0, 0.3 and 0.4 respectively. In the three bronchial carcinoids studied, two immunoreactive gastrin releasing peptide molecular weight forms were always found at Kav of 0.5 and 0.85 corresponding to gastrin releasing peptide and its fragment 1 4‐ 27 respectively. C onclusion Our results show that 7B2 and the two fragments of secretogranin 1 (GAWK and CCB) are the best biochemical markers of neuro‐endocrine differentiation in human lung tumours.