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, Aldo
AU - Papotti, Mauro
AU - Volante, M
AU - Sessa, Fausto
AU - Fazio, N
AU - Pruneri, G
AU - Rindi, G
AU - Solcia, E
AU - La Rosa, Stefano
AU - Capella, Carlo
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
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 -