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Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors.
Mod Pathol. 2005 Jun; 18(6):795-805.MP

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.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15578070

Citation

D'Adda, Tiziana, et al. "Malignancy-associated X Chromosome Allelic Losses in Foregut Endocrine Neoplasms: Further Evidence From Lung Tumors." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 18, no. 6, 2005, pp. 795-805.
D'Adda T, Bottarelli L, Azzoni C, et al. Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Mod Pathol. 2005;18(6):795-805.
D'Adda, T., Bottarelli, L., Azzoni, C., Pizzi, S., Bongiovanni, M., Papotti, M., Pelosi, G., Maisonneuve, P., Antonetti, T., Rindi, G., & Bordi, C. (2005). Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 18(6), 795-805.
D'Adda T, et al. Malignancy-associated X Chromosome Allelic Losses in Foregut Endocrine Neoplasms: Further Evidence From Lung Tumors. Mod Pathol. 2005;18(6):795-805. PubMed PMID: 15578070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. AU - D'Adda,Tiziana, AU - Bottarelli,Lorena, AU - Azzoni,Cinzia, AU - Pizzi,Silvia, AU - Bongiovanni,Massimo, AU - Papotti,Mauro, AU - Pelosi,Giuseppe, AU - Maisonneuve,Patrick, AU - Antonetti,Tommaso, AU - Rindi,Guido, AU - Bordi,Cesare, PY - 2004/12/4/pubmed PY - 2005/7/20/medline PY - 2004/12/4/entrez SP - 795 EP - 805 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod Pathol VL - 18 IS - 6 N2 - 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. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/15578070/Malignancy_associated_X_chromosome_allelic_losses_in_foregut_endocrine_neoplasms:_further_evidence_from_lung_tumors_ L2 - https://doi.org/10.1038/modpathol.3800353 DB - PRIME DP - Unbound Medicine ER -