Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_F2935414E8C8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.
Journal
Endocrine-related cancer
Author(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
Publication state
Published
Issued date
05/2018
Peer-reviewed
Oui
Volume
25
Number
5
Pages
583-593
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 (TP53, KRAS, BRAF) 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; P < 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, P = 0.04) was a weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11-2.32; P = 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.
Keywords
Carcinoma, Neuroendocrine/genetics, Carcinoma, Neuroendocrine/pathology, Cell Proliferation, Female, Humans, Ki-67 Antigen/genetics, Male, Prognosis, Ki67, MANEC, NEC, prognosis
Pubmed
Web of science
Open Access
Yes
Create date
06/04/2018 17:05
Last modification date
20/08/2019 17:19
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