Lung neuroendocrine tumors are catalogued in four categories by the World Health Organization (WHO 2004) classification. Its reproducibility and prognostic efficacy was disputed. The WHO 2010 classification of digestive neuroendocrine neoplasms is based on Ki67 proliferation assessment and proved prognostically effective. This study aims at comparing these two classifications and at defining a prognostic grading system for lung neuroendocrine tumors. The study included 399 patients who underwent surgery and with at least 1 year follow-up between 1989 and 2011. Data on 21 variables were collected, and performance of grading systems and their components was compared by Cox regression and multivariable analyses. All statistical tests were two-sided. At Cox analysis, WHO 2004 stratified patients into three major groups with statistically significant survival difference (typical carcinoid vs atypical carcinoid (AC), P=0.021; AC vs large-cell/small-cell lung neuroendocrine carcinomas, P<0.001). Optimal discrimination in three groups was observed by Ki67% (Ki67% cutoffs: G1 <4, G2 4-<25, G3 ≥25; G1 vs G2, P=0.021; and G2 vs G3, P≤0.001), mitotic count (G1 ≤2, G2 >2-47, G3 >47; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001), and presence of necrosis (G1 absent, G2 <10% of sample, G3 >10% of sample; G1 vs G2, P≤0.001; and G2 vs G3, P≤0.001) at uni and multivariable analyses. The combination of these three variables resulted in a simple and effective grading system. A three-tiers grading system based on Ki67 index, mitotic count, and necrosis with cutoffs specifically generated for lung neuroendocrine tumors is prognostically effective and accurate.
|Titolo:||Grading the neuroendocrine tumors of the lung: an evidence-based proposal|
|Parole Chiave:||Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Neuroendocrine; Child; Cohort Studies; Cross-Sectional Studies; Evidence-Based Medicine; Female; Humans; Italy; Kaplan-Meier Estimate; Ki-67 Antigen; Longitudinal Studies; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Proportional Hazards Models; Retrospective Studies; Tumor Markers, Biological; World Health Organization; Young Adult; Endocrinology; Oncology; Cancer Research; Endocrinology, Diabetes and Metabolism|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
Settore MED/21 - Chirurgia Toracica
|Data di pubblicazione:||feb-2014|
|Digital Object Identifier (DOI):||10.1530/ERC-13-0246|
|Appare nelle tipologie:||01 - Articolo su periodico|