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

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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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