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Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE)

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Nunez-Valdovinos, B
  • Carmona-Bayonas, A
  • Jimenez-Fonseca, P
  • Capdevila, J
  • Castano-Pascual, A
  • Benavent, M
  • Barrio, JJP
  • Teule, A
  • Alonso, V
  • Custodio, A
  • Marazuela, M
  • Beguiristain, A
  • Llanos, M
  • del Prado, MPM
  • Diaz-Perez, JA
  • Castellano, D
  • Sevilla, I
  • Lopez, C
  • Alonso, T
  • Garcia-Carbonero, R

Grupos

Abstract

Background. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. Subjects, Materials, and Methods. A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NETG2, NET-G3, NEC-G2, and NEC-G3. Results. Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). Conclusion. Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index.

Datos de la publicación

ISSN/ISSNe:
1083-7159, 1549-490X

ONCOLOGIST  OXFORD UNIV PRESS

Tipo:
Article
Páginas:
422-432
PubMed:
29330208
Factor de Impacto:
2,698 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 85

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Keywords

  • Gastroenteropancreatic; Neuroendocrine neoplasms; World Health Organization 2010; Ki-67; Tumor differentiation; Registry; Prognosis; Heterogeneity

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