The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms

Morphological Differentiation and Proliferation Identify Different Prognostic Categories

Massimo Milione, Patrick Maisonneuve, Francesca Spada, Alessio Pellegrinelli, Paola Spaggiari, Luca Albarello, Eleonora Pisa, Massimo Barberis, Alessandro Vanoli, Roberto Buzzoni, Sara Pusceddu, Laura Concas, Fausto Sessa, Enrico Solcia, Carlo Capella, Nicola Fazio, Stefano La Rosa

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background/Aims: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with >20% Ki-67 index 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 (G3) gastroenteropancreatic (GEP) neuroendocrine carcinomas (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: Univariable 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, Ki67 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 versus poorly-differentiated) and Ki67 index (

Original languageEnglish
JournalNeuroendocrinology
DOIs
Publication statusPublished - 2017

Fingerprint

Neuroendocrine Carcinoma
Neoplasms
DNA Mismatch Repair
Survival
Multivariate Analysis
Regression Analysis
Proteins

Keywords

  • Classification
  • Morphology
  • Neuroendocrine carcinoma
  • Prognosis
  • Proliferation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{774cb1402d8d45e28f324ea1a7f5ac13,
title = "The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories",
abstract = "Background/Aims: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with >20{\%} Ki-67 index 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 (G3) gastroenteropancreatic (GEP) neuroendocrine carcinomas (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: Univariable 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, Ki67 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 versus poorly-differentiated) and Ki67 index (",
keywords = "Classification, Morphology, Neuroendocrine carcinoma, Prognosis, Proliferation",
author = "Massimo Milione and Patrick Maisonneuve and Francesca Spada and Alessio Pellegrinelli and Paola Spaggiari and Luca Albarello and Eleonora Pisa and Massimo Barberis and Alessandro Vanoli and Roberto Buzzoni and Sara Pusceddu and Laura Concas and Fausto Sessa and Enrico Solcia and Carlo Capella and Nicola Fazio and {La Rosa}, Stefano",
year = "2017",
doi = "10.1159/000445165",
language = "English",
journal = "Neuroendocrinology",
issn = "0028-3835",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms

T2 - Morphological Differentiation and Proliferation Identify Different Prognostic Categories

AU - Milione, Massimo

AU - Maisonneuve, Patrick

AU - Spada, Francesca

AU - Pellegrinelli, Alessio

AU - Spaggiari, Paola

AU - Albarello, Luca

AU - Pisa, Eleonora

AU - Barberis, Massimo

AU - Vanoli, Alessandro

AU - Buzzoni, Roberto

AU - Pusceddu, Sara

AU - Concas, Laura

AU - Sessa, Fausto

AU - Solcia, Enrico

AU - Capella, Carlo

AU - Fazio, Nicola

AU - La Rosa, Stefano

PY - 2017

Y1 - 2017

N2 - Background/Aims: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with >20% Ki-67 index 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 (G3) gastroenteropancreatic (GEP) neuroendocrine carcinomas (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: Univariable 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, Ki67 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 versus poorly-differentiated) and Ki67 index (

AB - Background/Aims: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with >20% Ki-67 index 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 (G3) gastroenteropancreatic (GEP) neuroendocrine carcinomas (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: Univariable 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, Ki67 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 versus poorly-differentiated) and Ki67 index (

KW - Classification

KW - Morphology

KW - Neuroendocrine carcinoma

KW - Prognosis

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=84961231194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961231194&partnerID=8YFLogxK

U2 - 10.1159/000445165

DO - 10.1159/000445165

M3 - Article

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

ER -