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Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas
Author(s) -
Gugger Mathias,
Burckhardt Elisabeth,
Kappeler Andreas,
Hirsiger Hans,
Laissue Jean A.,
Mazzucchelli Luca
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1065
Subject(s) - biology , immunohistochemistry , carcinoma , cyclin d1 , pathology , fluorescence in situ hybridization , cancer research , carcinoid tumour , gene duplication , small cell lung carcinoma , retinoblastoma , neuroendocrine tumors , lung cancer , cancer , cell cycle , small cell carcinoma , gene , medicine , genetics , immunology , endocrinology , chromosome
The pathogenesis and interrelationships of neuroendocrine lung carcinomas are not well understood. Tissue macro‐arrays prepared from surgical resection specimens from 35 patients with typical carcinoid (TC), six with atypical carcinoid (AC), 13 with large cell neuroendocrine carcinoma (LCNEC), and 15 with small cell lung carcinoma (SCLC) were investigated by fluorescence in situ hybridization (FISH) and immunohistochemistry. Hybridizations with locus‐specific DNA probes demonstrated a high incidence of deletion for the tumour suppressor genes p53 and retinoblastoma (Rb), and for the oncogene cyclin D1, comparable in all carcinoma types. Similarly, an increase of DNA copy number for the Her‐2/neu and c‐myc oncogenes was noted in all neoplasms. A more detailed quantitative analysis of the results, however, demonstrated increasing numbers of cells harbouring these genomic alterations, from low‐grade TC to highly malignant SCLC, with the exception of cyclin D1 deletion. Mutations of the p53 and Rb genes, as assayed by immunohistochemical studies, were observed at high incidence in high‐grade carcinomas, compared with a low incidence in the low‐grade carcinomas. Conversely, in all carcinoma types, neither membrane‐bound Her‐2/neu nor nuclear cyclin D1 was detected. It is concluded that structural genomic alterations are frequent in neuroendocrine lung carcinomas and that their occurrence may be underestimated by immunohistochemical studies alone. The quantitative expansion of the Rb, p53, c‐myc, and Her‐2/neu alterations towards high‐grade carcinomas suggests common pathogenetic mechanisms in the spectrum of these neoplasms. Copyright © 2002 John Wiley & Sons, Ltd.