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A Subset of Large Cell Neuroendocrine Carcinomas in the Gastroenteropancreatic Tract May Evolve from Pre-existing Well-Differentiated Neuroendocrine Tumors.

Authors
  • Pelosi, Giuseppe1, 2
  • Bianchi, Fabrizio3
  • Dama, Elisa3
  • Metovic, Jasna4
  • Barella, Marco5
  • Sonzogni, Angelica6
  • Albini, Adriana7
  • Papotti, Mauro4
  • Gong, Yulan8
  • Vijayvergia, Namrata9
  • 1 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. [email protected] , (Italy)
  • 2 Inter-Hospital Pathology Division, IRCCS MultiMedica, Milan, Italy. [email protected] , (Italy)
  • 3 Cancer Biomarker Unit, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy. , (Italy)
  • 4 Department of Oncology, University of Turin, Turin, Italy. , (Italy)
  • 5 Inter-Hospital Pathology Division, IRCCS MultiMedica, Milan, Italy. , (Italy)
  • 6 Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. , (Italy)
  • 7 Laboratory of Vascular Biology and Angiogenesis, IRCCS MultiMedica, Milan, Italy. , (Italy)
  • 8 Department of Pathology, Fox Chase Cancer Centre, Philadelphia, PA, USA.
  • 9 Department of Medical Oncology, Fox Chase Cancer Centre, Philadelphia, PA, USA.
Type
Published Article
Journal
Endocrine Pathology
Publisher
Springer-Verlag
Publication Date
Sep 01, 2021
Volume
32
Issue
3
Pages
396–407
Identifiers
DOI: 10.1007/s12022-020-09659-6
PMID: 33433886
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In the gastro-entero-pancreatic (GEP) tract, neuroendocrine neoplasms (NENs) include well differentiated neuroendocrine tumors (NETs) and high-grade NE carcinomas (NECs), which are thought to make up separate and mutually exclusive tumor entities. Little is known, however, as to whether there may be any pathogenetic link between them. Clustering analysis of a 10-gene panel generated from a previously reported next-generation sequencing analysis on 48 GEP-NENs with clinical annotations was used in the study. Unsupervised cluster analysis showed three histology-independent clusters, namely, C1, C2, and C3, which accounted for 44% of patients but the entire array of mutations. All but two NECs fell into the clusters, yet with different prevalence rates (p < 0.0001). A model was devised according to which NETs were likely to evolve into NECs upon progression of C3 into C1 and C2, despite different morphology. The median Ki-67 labeling index was 5% in C3 showing better prognosis and 50% in C1 and C2 experiencing worse prognosis, with an impressive intra-tumor heterogeneity of diversely proliferating tumor areas. This study suggests that a subset of large cell NECs in the gastroenteropancreatic tract may evolve from pre-existing well-differentiated NETs. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

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