Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity.

Détails

ID Serval
serval:BIB_61FD6360EAC3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity.
Périodique
Endocrine-related Cancer
Auteur(s)
Sahnane N., Furlan D., Monti M., Romualdi C., Vanoli A., Vicari E., Solcia E., Capella C., Sessa F., La Rosa S.
ISSN
1479-6821 (Electronic)
ISSN-L
1351-0088
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
22
Numéro
1
Pages
35-45
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs) are heterogeneous neoplasms characterized by poor outcome. Microsatellite instability (MSI) has recently been found in colorectal NECs showing a better prognosis than expected. However, the frequency of MSI in a large series of GEP-NEC/MANECs is still unknown. In this work, we investigated the incidence of MSI in GEP-NEC/MANECs and characterized their clinicopathologic and molecular features. MSI analysis and immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were performed in 89 GEP-NEC/MANECs (six esophageal, 77 gastrointestinal, three pancreatic, and three of the gallbladder). Methylation of 34 genes was studied by methylation-specific multiplex ligation probe amplification. Mutation analysis of BRAF and KRAS was assessed by PCR-pyrosequencing analysis. MSI was observed in 11 NEC/MANECs (12.4%): seven intestinal and four gastric. All but two MSI-cases showed MLH1 methylation and loss of MLH1 protein. The remaining two MSI-cancers showed lack of MSH2 or PMS2 immunohistochemical expression. MSI-NEC/MANECs showed higher methylation levels than microsatellite stable NEC/MANECs (40.6% vs 20.2% methylated genes respectively, P<0.001). BRAF mutation was detected in six out of 88 cases (7%) and KRAS mutation was identified in 15 cases (17%). BRAF mutation was associated with MSI (P<0.0008), while KRAS status did not correlate with any clinicopathologic or molecular feature. Vascular invasion (P=0.0003) and MSI (P=0.0084) were identified as the only independent prognostic factors in multivariate analysis. We conclude that MSI identifies a subset of gastric and intestinal NEC/MANECs with distinct biology and better prognosis. MSI-NEC/MANECs resemble MSI-gastrointestinal adenocarcinomas for frequency, molecular profile and pathogenetic mechanisms.
Mots-clé
Adult, Aged, Aged, 80 and over, Carcinoma, Neuroendocrine/genetics, Carcinoma, Neuroendocrine/pathology, Cohort Studies, DNA Methylation, DNA Mismatch Repair, Female, Gastrointestinal Neoplasms/genetics, Gastrointestinal Neoplasms/pathology, Humans, Male, Microsatellite Instability, Middle Aged
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2016 11:55
Dernière modification de la notice
20/08/2019 14:18
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