Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis

M. Milione, P. Maisonneuve, A. Pellegrinelli, F. Grillo, L. Albarello, P. Spaggiari, A. Vanoli, G. Tagliabue, E. Pisa, L. Messerini, G. Centonze, F. Inzani, A. Scarpa, M. Papotti, M. Volante, F. Sessa, N. Fazio, G. Pruneri, G. Rindi, E. SolciaS.L. Rosa, C. Capella

Research output: Contribution to journalArticle

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
Original languageEnglish
Pages (from-to)583-593
Number of pages11
JournalEndocrine-Related Cancer
Volume25
Issue number5
DOIs
Publication statusPublished - 2018

Fingerprint

Carcinoma
Neuroendocrine Carcinoma
Digestive System
DNA Mismatch Repair
Survival
beta Catenin
Neoplasms
Confidence Intervals
Proteins

Keywords

  • aldehyde dehydrogenase
  • antineoplastic agent
  • B Raf kinase
  • beta catenin
  • K ras protein
  • Ki 67 antigen
  • mismatch repair protein
  • protein bcl 2
  • protein p16
  • protein p53
  • stem cell factor receptor, adult
  • aged
  • Article
  • cancer diagnosis
  • cancer localization
  • cancer mortality
  • cancer prognosis
  • cancer risk
  • cancer staging
  • cancer survival
  • cell proliferation
  • clinical feature
  • controlled study
  • female
  • human
  • immunohistochemistry
  • immunophenotyping
  • major clinical study
  • male
  • mixed adenoneuroendocrine carcinoma
  • multicenter study
  • neoadjuvant chemotherapy
  • overall survival
  • retrospective study

Cite this

Milione, M., Maisonneuve, P., Pellegrinelli, A., Grillo, F., Albarello, L., Spaggiari, P., ... Capella, C. (2018). Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis. Endocrine-Related Cancer, 25(5), 583-593. https://doi.org/10.1530/ERC-17-0557

Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis. / 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.; Rosa, S.L.; Capella, C.

In: Endocrine-Related Cancer, Vol. 25, No. 5, 2018, p. 583-593.

Research output: Contribution to journalArticle

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, Rosa, SL & Capella, C 2018, 'Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis', Endocrine-Related Cancer, vol. 25, no. 5, pp. 583-593. https://doi.org/10.1530/ERC-17-0557
Milione M, Maisonneuve P, Pellegrinelli A, Grillo F, Albarello L, Spaggiari P et al. Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis. Endocrine-Related Cancer. 2018;25(5):583-593. https://doi.org/10.1530/ERC-17-0557
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. ; Rosa, S.L. ; Capella, C. / Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis. In: Endocrine-Related Cancer. 2018 ; Vol. 25, No. 5. pp. 583-593.
@article{d40bade4d9c44ff8b61accd0d4760e98,
title = "Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis",
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",
keywords = "aldehyde dehydrogenase, antineoplastic agent, B Raf kinase, beta catenin, K ras protein, Ki 67 antigen, mismatch repair protein, protein bcl 2, protein p16, protein p53, stem cell factor receptor, adult, aged, Article, cancer diagnosis, cancer localization, cancer mortality, cancer prognosis, cancer risk, cancer staging, cancer survival, cell proliferation, clinical feature, controlled study, female, human, immunohistochemistry, immunophenotyping, major clinical study, male, mixed adenoneuroendocrine carcinoma, multicenter study, neoadjuvant chemotherapy, overall survival, retrospective study",
author = "M. Milione and P. Maisonneuve and A. Pellegrinelli and F. Grillo and L. Albarello and P. Spaggiari and A. Vanoli and G. Tagliabue and E. Pisa and L. Messerini and G. Centonze and F. Inzani and A. Scarpa and M. Papotti and M. Volante and F. Sessa and N. Fazio and G. Pruneri and G. Rindi and E. Solcia and S.L. Rosa and C. Capella",
note = "cited By 5",
year = "2018",
doi = "10.1530/ERC-17-0557",
language = "English",
volume = "25",
pages = "583--593",
journal = "Endocrine-Related Cancer",
issn = "1351-0088",
publisher = "BioScientifica Ltd.",
number = "5",

}

TY - JOUR

T1 - Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis

AU - Milione, M.

AU - Maisonneuve, P.

AU - Pellegrinelli, A.

AU - Grillo, F.

AU - Albarello, L.

AU - Spaggiari, P.

AU - Vanoli, A.

AU - Tagliabue, G.

AU - Pisa, E.

AU - Messerini, L.

AU - Centonze, G.

AU - Inzani, F.

AU - Scarpa, A.

AU - Papotti, M.

AU - Volante, M.

AU - Sessa, F.

AU - Fazio, N.

AU - Pruneri, G.

AU - Rindi, G.

AU - Solcia, E.

AU - Rosa, S.L.

AU - Capella, C.

N1 - cited By 5

PY - 2018

Y1 - 2018

N2 - 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

AB - 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

KW - aldehyde dehydrogenase

KW - antineoplastic agent

KW - B Raf kinase

KW - beta catenin

KW - K ras protein

KW - Ki 67 antigen

KW - mismatch repair protein

KW - protein bcl 2

KW - protein p16

KW - protein p53

KW - stem cell factor receptor, adult

KW - aged

KW - Article

KW - cancer diagnosis

KW - cancer localization

KW - cancer mortality

KW - cancer prognosis

KW - cancer risk

KW - cancer staging

KW - cancer survival

KW - cell proliferation

KW - clinical feature

KW - controlled study

KW - female

KW - human

KW - immunohistochemistry

KW - immunophenotyping

KW - major clinical study

KW - male

KW - mixed adenoneuroendocrine carcinoma

KW - multicenter study

KW - neoadjuvant chemotherapy

KW - overall survival

KW - retrospective study

U2 - 10.1530/ERC-17-0557

DO - 10.1530/ERC-17-0557

M3 - Article

VL - 25

SP - 583

EP - 593

JO - Endocrine-Related Cancer

JF - Endocrine-Related Cancer

SN - 1351-0088

IS - 5

ER -