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

Details

Serval ID
serval:BIB_91838CB79DC5
Type
Article: article from journal or magazin.
Collection
Publications
Title
Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors.
Journal
Modern Pathology
Author(s)
D'Adda T., Bottarelli L., Azzoni C., Pizzi S., Bongiovanni M., Papotti M., Pelosi G., Maisonneuve P., Antonetti T., Rindi G., Bordi C.
ISSN
0893-3952 (Print)
ISSN-L
0893-3952
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
18
Number
6
Pages
795-805
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Association of X chromosome allelic losses with tumor malignancy has been identified in foregut but not in midgut endocrine neoplasms. The aim of this study was to investigate the association of deletions on X chromosome with malignancy in lung neuroendocrine tumors, another family of foregut neoplasms comprising four categories with increased malignancy: typical and atypical carcinoids, large cell neuroendocrine and small cell lung carcinomas. To evaluate loss of heterozygosity, DNA extracted from nine typical carcinoids, 17 atypical carcinoids, six large cell neuroendocrine carcinomas and five small cell lung carcinomas was PCR-amplified for 18 microsatellite markers spanning the whole X chromosome. All tissue samples were formalin-fixed and paraffin-embedded. X chromosome losses were absent in typical carcinoids, whereas they were found in nine out of 17 atypical carcinoids and in five out of six large cell neuroendocrine carcinomas (involving 28 and 70% of informative loci, respectively). On the contrary, deletions on X chromosome were an extremely rare event in small cell lung carcinomas. In atypical carcinoids, the presence of losses was associated with larger tumor size, higher pT status and advanced stage. No death occurred in atypical carcinoid patients without deletions on X chromosome, whereas all atypical carcinoid patients who had died from disease showed allelic losses. In conclusion, X chromosome allelic losses, absent in benign 'typical' carcinoids, progressively increased in frequency from intermediate-grade 'atypical' carcinoids to high-grade large cell neuroendocrine carcinomas. These results extend the association of deletions on X chromosome with malignancy, already demonstrated in other foregut endocrine neoplasms, to lung neuroendocrine tumors. The absence of X chromosome allelic losses in small cell lung carcinomas underlines a striking difference from large cell neuroendocrine carcinomas, possibly linked to different pathogenetic mechanisms of these two highly aggressive neuroendocrine lung tumors.
Keywords
Adult, Aged, Carcinoid Tumor/genetics, Carcinoid Tumor/pathology, Carcinoma, Large Cell/genetics, Carcinoma, Large Cell/pathology, Carcinoma, Small Cell/genetics, Carcinoma, Small Cell/pathology, Chromosomes, Human, X/genetics, Female, Humans, Loss of Heterozygosity, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Microsatellite Repeats, Middle Aged, Neuroendocrine Tumors/genetics, Neuroendocrine Tumors/pathology, Survival Analysis
Pubmed
Web of science
Open Access
Yes
Create date
05/02/2015 14:29
Last modification date
20/08/2019 14:54
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