Ki-67 Index of 55% Distinguishes Two Groups of Bronchopulmonary Pure and Composite Large Cell Neuroendocrine Carcinomas with Distinct Prognosis.

Carcinoma, Large Cell / diagnosis Carcinoma, Neuroendocrine / diagnosis Humans Ki-67 Antigen / metabolism Lung Neoplasms / diagnosis Prognosis Survival Analysis
Combined large cell neuroendocrine carcinoma Ki-67 index Large cell neuroendocrine carcinoma Napsin A

Journal

Neuroendocrinology
ISSN: 1423-0194
Titre abrégé: Neuroendocrinology
Pays: Switzerland
ID NLM: 0035665

Informations de publication

Date de publication:
2021
Historique:
received: 07 01 2020
accepted: 01 05 2020
pubmed: 5 5 2020
medline: 18 11 2021
entrez: 5 5 2020
Statut: ppublish

Résumé

Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation. Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component. A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index <55% (LCNEC-A) and 77 had a Ki-67 index ≥55% (LCNEC-B). Statistically significant differences in OS (log-rank p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05). The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.

Sections du résumé

BACKGROUND
Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation.
METHODS
Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component.
RESULTS
A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index <55% (LCNEC-A) and 77 had a Ki-67 index ≥55% (LCNEC-B). Statistically significant differences in OS (log-rank p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05).
CONCLUSIONS
The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.

Identifiants

DOI: 10.1159/000508376 PMID: 32365350
pubmed: 32365350
pii: 000508376
doi: 10.1159/000508376
doi:

Substances chimiques

Ki-67 Antigen 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

475-489

Informations de copyright

© 2020 S. Karger AG, Basel.

Auteurs

Massimo Milione (M)

First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy, Massimo.milione@istitutotumori.mi.it.

Patrick Maisonneuve (P)

Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Federica Grillo (F)

Unit of Pathology, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy.

Alessandro Mangogna (A)

Unit of Pathology, Clinical Department of Medical, Surgical and Health Science, University of Trieste, Ospedale di Cattinara, Trieste, Italy.

Giovanni Centonze (G)

First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Natalie Prinzi (N)

Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Sara Pusceddu (S)

Medical Oncology Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Giovanna Garzone (G)

First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Laura Cattaneo (L)

First Division of Pathology, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Adele Busico (A)

2nd Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

Paola Bossi (P)

Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy.

Paola Spaggiari (P)

Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy.

Alessio Pellegrinelli (A)

Department of Pathology, ASST Franciacorta, Mellino Mellini Hospital, Brescia, Italy.

Alessandro Del Gobbo (A)

Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Stefano Ferrero (S)

Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Biomedical Surgical and Dental Sciences, University of Milan, Milan, Italy.

Ketevani Kankava (K)

Teaching, Scientific and Diagnostic Pathology Laboratory, Tbilisi State Medical University, Tbilisi, Georgia.

Giancarlo Pruneri (G)

2nd Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
School of Medicine, University of Milan, Milan, Italy.

Luigi Rolli (L)

Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Elisa Roca (E)

Medical Oncology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy.

Luisa Bercich (L)

Department of Pathology, ASST Spedali Civili of Brescia, Brescia, Italy.

Andrea Tironi (A)

Department of Pathology, ASST Spedali Civili of Brescia, Brescia, Italy.

Mauro Roberto Benvenuti (MR)

Thoracic Surgery Unit, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, Medical Oncology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Maria Sole Gallazzi (MS)

Thoracic Surgery Unit, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, Medical Oncology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Rosalia Romano (R)

Thoracic Surgery Unit, Department of Medical and Surgical Specialties Radiological Sciences and Public Health, Medical Oncology, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.

Alfredo Berruti (A)

Medical Oncology Unit, ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiological Science and Public Health, University of Brescia, Brescia, Italy.

Ugo Pastorino (U)

Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Carlo Capella (C)

Unit of Pathology, Department of Medicine and Surgery and Research Center for the Study of Hereditary and Familial tumors, University of Insubria, Varese, Italy.

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Carcinome à grandes cellules › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroendocrines › Carcinome neuroendocrine › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Antigène KI-67 › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Diagnostic › Pronostic › Ki-67 Index of 55% Distinguishes Two Groups of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Ki-67 Index of 55% Distinguishes Two Groups of...