Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.

Détails

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Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_F2935414E8C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.
Périodique
Endocrine-related cancer
Auteur(s)
Milione M., Maisonneuve P., Pellegrinelli A., Grillo F., Albarello L., Spaggiari P., Vanoli A., Tagliabue G., Pisa E., Messerini L., Centonze G., Inzani F., Scarpa A., Papotti M., Volante M., Sessa F., Fazio N., Pruneri G., Rindi G., Solcia E., La Rosa S., Capella C.
ISSN
1479-6821 (Electronic)
ISSN-L
1351-0088
Statut éditorial
Publié
Date de publication
05/2018
Peer-reviewed
Oui
Volume
25
Numéro
5
Pages
583-593
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin, Bcl-2, p16, Rb1, ALDH, mismatch repair proteins and CD117) were investigated separately in both components, genomic ( <i>TP53</i> , <i>KRAS</i> , <i>BRAF</i> ) alterations were searched for on the entire tumor. Data were correlated with overall survival (OS). MANEC sites were: 92 colorectal, 44 gastroesophageal and 24 pancreatobiliary. Median OS was 13.2 months. After adjustment for primary site, Ki67 index of the NEC component (but not of the non-NEC component) was the most powerful prognostic marker. At multivariable analysis, patients with Ki67 ≥ 55% had an 8-fold risk of death (hazard ratio (HR) 7.83; 95% confidence interval (CI) 4.17-14.7; <i>P</i>  < 0.0001) and a median OS of 12.2 months compared to those with Ki67 < 55% (median OS 40.5 months). MC (HR 1.51; 95% CI 1.03-2.20, <i>P</i>  = 0.04) was a weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11-2.32; <i>P</i>  = 0.01) was significantly associated with poorer survival. No single immunomarker, in either component, was statistically significant. This retrospective analysis of a large series of digestive system MANECs, showed that the NEC component, particularly its Ki67 index, was the main prognostic driver.
Mots-clé
Ki67, MANEC, NEC, prognosis
Pubmed
Web of science
Création de la notice
06/04/2018 17:05
Dernière modification de la notice
18/07/2018 7:09
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