Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 583-593 |
| Number of pages | 11 |
| Journal | Endocrine-Related Cancer |
| Volume | 25 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2018 |
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Keywords
- Ki67
- MANEC
- NEC
- Prognosis
- 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
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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 journal › Article
}
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 Export Date: 5 February 2019 CODEN: ERCAE Correspondence Address: Milione, M.; 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei TumoriItaly; email: massimo.milione@istitutotumori.mi.it Chemicals/CAS: aldehyde dehydrogenase, 37353-37-0, 9028-86-8; protein bcl 2, 219306-68-0 Funding details: Università degli Studi di Pavia Funding details: Fondazione IRCCS Policlinico San Matteo Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC, IG 2013 14696 Funding text 1: Aldo Scarpa is supported by AIRC 5 × 1000 n. 18182. Guido Rindi is supported by internal university grants (Università Cattolica line D.1 2015-R412500333 and D.1/2016-R412500403) and by the Associazione Italiana Ricerca sul Cancro – AIRC IG 2013 14696. Institutional support by: Fondazione IRCCS Istituto Nazionale Tumori Milano, Italy; European Institute of Oncology (IEO), Milan, Italy; Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy; IRCCS San Raffaele Scientific Institute, Milan, Italy; Cancer Center Humanitas, Milan, Italy; this research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. References: Ali, A.S., Gronberg, M., Federspiel, B., Scoazec, J.Y., Hjortland, G.O., Gronbaek, H., Ladekarl, M., Vestermark, L.W., Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma (2017) PLoS ONE, 12, p. e0187667. , https://doi.org/10.1371/journal.pone.0187667; Amin, M.B., (2017) AJCC Cancer Staging Manual 8th Edition, , Chicago, IL, USA: AJCC; Bosman, F.T., Carneiro, F., Hruban, R., Theise, N., (2010) WHO Classification of Tumours of The Digestive System, , Lyon, France: IARC Press; Chiaravalli, A.M., Furlan, D., Facco, C., Tibiletti, M.G., Dionigi, A., Casati, B., Albarello, L., Capella, C., Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences (2001) Virchows Archiv, 438, pp. 39-48. , https://doi.org/10.1007/s004280000325; Furlan, D., Cerutti, R., Genasetti, A., Pelosi, G., Uccella, S., La Rosa, S., Capella, C., Microallelotyping defines the monoclonal or the polyclonal origin of mixed and collision endocrine-exocrine tumors of the gut (2003) Laboratory Investigation, 83, pp. 963-971. , https://doi.org/10.1097/01.LAB.0000079006.91414.BE; Furlan, D., Sahnane, N., Mazzoni, M., Pastorino, R., Carnevali, I., Stefanoli, M., Ferretti, A., Capella, C., Diagnostic utility of MS-MLPA in DNA methylation profiling of adenocarcinomas and neuroendocrine carcinomas of the colon-rectum (2013) Virchows Archiv, 462, pp. 47-56. , https://doi.org/10.1007/s00428-012-1348-2; Huang, J., Behrens, C., Wistuba, I.I., Gazdar, A.F., Jagirdar, J., Clonality of combined tumors (2002) Archives of Pathology and Laboratory Medicine, 126, pp. 437-441. , https://doi.org/10.1043/00039985(2002)126<0437:COCT>2.0.CO;2; Jesinghaus, M., Konukiewitz, B., Keller, G., Kloor, M., Steiger, K., Reiche, M., Penzel, R., Hermann, G., Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas (2017) Modern Pathology, 30, pp. 610-619. , https://doi.org/10.1038/modpathol.2016.220; Kim, K.M., Kim, M.J., Cho, B.K., Choi, S.W., Rhyu, M.G., Genetic evidence for the multi-step progression of mixed glandular-neuroendocrine gastric carcinomas (2002) Virchows Archiv, 440, pp. 85-93. , https://doi.org/10.1007/s004280100540; Kloppel, G., Neuroendocrine neoplasms: Dichotomy, origin and classifications (2017) Visceral Medicine, 33, pp. 324-330. , https://doi.org/10.1159/000481390; Konukiewitz, B., Schlitter, A.M., Jesinghaus, M., Pfister, D., Steiger, K., Segler, A., Agaimy, A., Weichert, W., Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20 (2017) Modern Pathology, 30, pp. 587-598. , https://doi.org/10.1038/modpathol.2016.217; La Rosa, S., Adsay, V., Albarello, L., Asioli, S., Casnedi, S., Franzi, F., Marando, A., Vanoli, A., 2012a Clinicopathologic study of 62 acinar cell carcinomas of the pancreas: Insights into the morphology and immunophenotype and search for prognostic markers American Journal of Surgical Pathology, 36, pp. 1782-1795. , https://doi.org/10.1097/PAS.0b013e318263209d; La Rosa, S., Marando, A., Furlan, D., Sahnane, N., Capella, C., Colorectal poorly differentiated neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas: Insights into the diagnostic immunophenotype, assessment of methylation profile, and search for prognostic markers (2012) American Journal of Surgical Pathology, 36, pp. 601-611. , https://doi.org/10.1097/PAS.0b013e318242e21c; La Rosa, S., Marando, A., Sessa, F., Capella, C., Mixed adenoneuroendocrine carcinomas (MANECs) of the gastrointestinal tract: An update (2012) Cancers, 4, pp. 11-30. , https://doi.org/10.3390/cancers4010011; Lugli, A., Kirsch, R., Ajioka, Y., Bosman, F., Cathomas, G., Dawson, H., El Zimaity, H., Hartmann, A., Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016 (2017) Modern Pathology, 30, pp. 1299-1311. , https://doi.org/10.1038/modpathol.2017.46; Meazza, C., Belfiore, A., Busico, A., Settanni, G., Paielli, N., Cesana, L., Ferrari, A., Gronchi, A., AKT1 and BRAF mutations in pediatric aggressive fibromatosis (2016) Cancer Medicine, 5, pp. 1204-1213. , https://doi.org/10.1002/cam4.669; Milione, M., Maisonneuve, P., Spada, F., Pellegrinelli, A., Spaggiari, P., Albarello, L., Pisa, E., Buzzoni, R., The clinicopathologic heterogeneity of grade 3 gastroenteropancreatic neuroendocrine neoplasms: Morphological differentiation and proliferation identify different prognostic categories (2017) Neuroendocrinology, 104, pp. 85-93. , https://doi.org/10.1159/000445165; Ohike, N.A., La Rosa, S., Volante, M., Zamboni, G., (2017) Mixed Neuroendocrine-Non Neuroendocrine Neoplasms, , Lyon, France: IARC Press; Paniz Mondolfi, A.E., Slova, D., Fan, W., Attiyeh, F.F., Afthinos, J., Reidy, J., Pang, Y., Theise, N.D., Mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder: A possible stem cell tumor? (2011) Pathology International, 61, pp. 608-614. , https://doi.org/10.1111/j.1440-1827.2011.02709.x; Rindi, G., Arnold, R., Bosman, F.T., Capella, C., Klimstra, D.S., KlÖppel, G., Komminoth, P., Solcia, E., (2010) Nomenclature and Classification of Digestive Neuroendocrine Tumours, , Eds TF Bosman, F Carneiro, RH Hruban & ND Theise. Lyon, France: IARC Press; Sahnane, N., Furlan, D., Monti, M., Romualdi, C., Vanoli, A., Vicari, E., Solcia, E., La Rosa, S., Microsatellite unstable gastroinestinal neuroendocrin e carcinomas: A new clinicopathologic entity (2015) Endocrine-Related Cancer, 22, pp. 35-45. , https://doi.org/10.1530/ERC-14-0410; Scardoni, M., Vittoria, E., Volante, M., Rusev, B., Bersani, S., Mafficini, A., Gottardi, M., Butturini, G., Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract: Targeted next-generation sequencing suggests a monoclonal origin of the two components (2014) Neuroendocrinology, 100, pp. 310-316. , https://doi.org/10.1159/000369071; Shafqat, H., Ali, S., Salhab, M., Olszewski, A.J., Survival of patients with neuroendocrine carcinoma of the colon and rectum: A population-based analysis (2015) Diseases of The Colon and Rectum, 58, pp. 294-303. , https://doi.org/10.1097/DCR.0000000000000298; Sorbye, H., Welin, S., Langer, S.W., Vestermark, L.W., Holt, N., Osterlund, P., Dueland, S., Ohrling, K., Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study (2013) Annals of Oncology, 24, pp. 152-160. , https://doi.org/10.1093/annonc/mds276; Volante, M., Brizzi, M.P., Faggiano, A., La Rosa, S., Rapa, I., Ferrero, A., Mansueto, G., Capella, C., Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: A proposal of scoring system correlated with somatostatin receptor scintigraphy (2007) Modern Pathology, 20, pp. 1172-1182. , https://doi.org/10.1038/modpathol.3800954; Volante, M., Monica, V., Birocco, N., Brizzi, M.P., Busso, S., Daniele, L., La Rosa, S., Berruti, A., Expression analysis of genes involved in DNA repair or synthesis in mixed neuroendocrine/nonneuroendocrine carcinomas (2015) Neuroendocrinology, 101, pp. 151-160. , https://doi.org/10.1159/000375449; Vortmeyer, A.O., Lubensky, I.A., Merino, M.J., Wang, C.Y., Pham, T., Furth, E.E., Zhuang, Z., Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas (1997) Journal of The National Cancer Institute, 89, pp. 1448-1453. , https://doi.org/10.1093/jnci/89.19.1448; Woischke, C., Schaaf, C.W., Yang, H.M., Vieth, M., Veits, L., Geddert, H., Markl, B., Frolich, M., In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components (2017) Modern Pathology, 30, pp. 95-103. , https://doi.org/10.1038/modpathol.2016.150; Xie, J.W., Lu, J., Lin, J.X., Zheng, C.H., Li, P., Wang, J.B., Chen, Q.Y., Tu, R.H., Different long-term oncologic outcomes after radical surgical resection for neuroendocrine carcinoma and adenocarcinoma of the stomach (2017) Oncotarget, 8, pp. 57495-57504. , https://doi.org/10.18632/oncotarget.15488
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 - Ki67
KW - MANEC
KW - NEC
KW - Prognosis
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
KW - 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 -