Microsatellite unstable gastrointestinal neuroendocrine carcinomas: A new clinicopathologic entity

Nora Sahnane, Daniela Furlan, Matilde Monti, Chiara Romualdi, Alessandro Vanoli, Emanuela Vicari, Enrico Solcia, Carlo Capella, Fausto Sessa, Stefano La Rosa

Research output: Contribution to journalArticlepeer-review


Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) and mixed adenoneuro-endocrine 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

Original languageEnglish
Pages (from-to)35-45
Number of pages11
JournalEndocrine-Related Cancer
Issue number1
Publication statusPublished - Feb 1 2015


  • Gene methylation
  • Microsatellite instability
  • Mismatch repair
  • NEC
  • Neuroendocrine carcinomas

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)


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