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; Aldo Scarpa; Mauro Papotti; M Volante; Fausto Sessa; N Fazio; G Pruneri; G Rindi; E Solcia; Stefano La Rosa; Carlo Capella

doi:10.1530/ERC-17-0557

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, Aldo Scarpa, Mauro Papotti, M Volante, Fausto Sessa, N Fazio, G Pruneri, G Rindi, E SolciaStefano La Rosa, Carlo Capella

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	583-593
Number of pages	11
Journal	Endocrine-Related Cancer
Volume	25
Issue number	5
DOIs	https://doi.org/10.1530/ERC-17-0557
Publication status	Published - 2018

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

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

Research output: Contribution to journal › Article

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 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 ; Vanoli, A ; Tagliabue, G ; Pisa, E ; Messerini, L ; Centonze, G ; Inzani, F ; Scarpa, Aldo ; Papotti, Mauro ; Volante, M ; Sessa, Fausto ; Fazio, N ; Pruneri, G ; Rindi, G ; Solcia, E ; La Rosa, Stefano ; Capella, Carlo. / Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis. In: Endocrine-Related Cancer. 2018 ; Vol. 25, No. 5. pp. 583-593.

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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",

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 Aldo Scarpa and Mauro Papotti and M Volante and Fausto Sessa and N Fazio and G Pruneri and G Rindi and E Solcia and {La Rosa}, Stefano and Carlo Capella",

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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

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