The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories

M. Milione, P. Maisonneuve, F. Spada, A. Pellegrinelli, P. Spaggiari, L. Albarello, E. Pisa, M. Barberis, A. Vanoli, R. Buzzoni, S. Pusceddu, L. Concas, F. Sessa, E. Solcia, C. Capella, N. Fazio, S. La Rosa

Research output: Contribution to journalArticle

Abstract

BACKGROUND/AIMS: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS). METHODS: Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features. RESULTS: With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (/=55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p /=55% (type C). CONCLUSIONS: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.
Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalNeuroendocrinology
Volume104
Issue number1
DOIs
Publication statusPublished - 2017

Keywords

  • Antineoplastic Agents/therapeutic use
  • Carcinoma, Neuroendocrine/drug therapy/mortality/pathology
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Humans
  • Ion Channels/metabolism
  • Ki-67 Antigen/metabolism
  • Male
  • Neuroendocrine Tumors/drug therapy/mortality/pathology
  • Pancreatic Neoplasms/drug therapy/mortality/pathology
  • Proto-Oncogene Proteins c-kit/metabolism
  • Regression Analysis
  • Survival Analysis

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