The position of pulmonary carcinoids within the spectrum of neuroendocrine tumors of the lung and other tissues

Abstract

Bronchopulmonary carcinoids comprise 25% of all human carcinoids. The World Health Organization divides them into typical (TC) and atypical forms (ATC), distinguished by differences in mitotic counts lower or higher than 2/2 mm(2) and the presence or absence of necrosis. The reproducibility of this classification with respect to the borderline cases with 1-2 mitotic counts/2 mm(2) has been questioned. We have analyzed 15 TCs and 20 ATCs by comparative genomic hybridization. Loss of 11q was the most frequent aberration in ATC (55%), but was observed only twice in TC (13%). Deletions of 3p were seen only in ATC (25%). Meta-analysis of our data and data from 218 neuroendocrine tumors and 50 non-small-cell lung carcinomas obtained from the literature revealed differences between carcinoids and carcinomas. For example, loss of 5q is frequent in lung carcinomas (75%) but is rarely seen in carcinoids (1.4%). Deletions of 11q are less frequent in neuroendocrine lung carcinomas than in ATC. To obtain a more objective survey of the relationship of pulmonary carcinoids to other neuroendocrine tumors and lung carcinomas, we created a hierarchical clustering dendrogram. This statistical approach resulted in a clear separation of carcinoids and carcinomas, which both built up different clusters. In summary, this study demonstrates the benefit of chromosomal analysis supplementary to the diagnosis of bronchopulmonary carcinoids. We also identified the feasibility of hierarchical clustering to get some clues on relationship between different tumor types. This study further argues against a transition of ATC to high-grade neuroendocrine lung carcinoma.

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

“…These results are in keeping with previous observations of a progressive accumulation of genetic defects from low-to high-grade neuroendocrine lung neoplasms. 8,9 Although a transition of either typical or atypical carcinoids to high-grade neuroendocrine carcinomas is currently deemed to be unlikely, 10 we herein indicate that carcinoids and large cell neuroendocrine carcinomas may share common genetic alterations on X chromosome, suggesting a critical role for these chromosomal regions in the pathogenesis of both tumors. Moreover, the finding of several X chromosome LOH in large cell neuroendocrine carcinomas but not in small cell lung carcinomas supports the view that these highly aggressive lung neuroendocrine carcinomas are genetically different.…”

Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

“…Using conventional CGH techniques, comparative analyses of the genomic differences among SCLC, bronchial carcinoids, and GI carcinoids have been conducted (41)(42)(43). Through comparison of bronchial carcinoids and SCLCs, Ullmann et al (41) found that carcinoids carried fewer chromosomal aberrancies than SCLC tumors and that SCLC tumors were characterized by many gains and losses in their genome.…”

Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: A novel approach using real-time PCR with melting curve analysis in histopathologic material

“…In pulmonary carcinoids, an interesting subset of endocrine tumors, similar MEN1 alterations have been reported and considered to be involved in the development of these tumors (17)(18)(19)(20)(21)(22)(23).…”

“…Alterations of the MEN1 gene occur in a great variety of endocrine tumors and they are considered also to be involved in the pathogenesis of pulmonary carcinoids (17)(18)(19)(20)(21)(22)(23)(24). Specifically, allelic deletions and mutations of the MEN1 gene have been reported in lung carcinoid tumors, including those developing sporadically in the absence of MEN1 syndrome (17,20,24).…”