457P - Predictive factors in GEP-NEN: the integrated role of Ki67, beta-catenin and morphology

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Neuroendocrine Cancers
Endocrine Cancers
Citation Annals of Oncology (2017) 28 (suppl_5): v142-v157. 10.1093/annonc/mdx368
Authors M. MILIONE1, R. Miceli2, A. Pellegrinelli1, G. Centonze1, F. Barretta2, S. Pusceddu3, L. Giacomelli4, J. Coppa5, V. Mazzaferro6, G. Sozzi7, A. Anichini8, F. de Braud3
  • 1Pathology And Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 2Department Of Medical Statistics, Biometry And Bioinformatics, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4Department Of Surgical Sciences And Integrated Diagnostic, University of Genova, 20133 - Genoa/IT
  • 5Surgery, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 6Departments Of Surgery, Liver Transplantation And Gastroenterology, Fondazione Istituto Nazionale Tumori (National Cancer Institute) IRCCS, Milan/IT
  • 7Experimental, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 8Immunotherapy Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano/IT



The WHO 2010 classification divides gastro-entero-pancreatic neoplasms (GEP-NENs) into G1, G2 and G3, according to Ki67 and/or mitotic index. Several studies have proposed to further divide G3 diseases in at least two subgroups, defined by Ki67 and/or morphological features. We investigated the morphological or immunohistochemical features associated with poorer prognosis and weather the G3 category could be further divided according to such features.


We evaluated 314 consecutive GEP-NEN patients. Surgical specimens of primitive tumors were assessed for morphology (m0: well-differentiated; m1: poorly-differentiated), Ki67 and beta-catenin (B01 absent or not-nuclear localization; B2 nuclear localization). Those features were correlated with overall survival (OS) and disease-free survival (DFS) after surgery by means of Cox multivariable models. The model performance was evaluated by means of Harrell’s C index.


Median follow-up was 84 months (95% CI: 74-103). Based on Ki67 only, the WHO 2010 classification allowed to distinguish three classes with different prognosis (5-year OS: ≤2%: 97.0%, 2-20%: 90.9%, >20%: 14.5%). When considering Ki67 as continuous variable, and by including also morphology and beta-catenin in the multivariable OS model, patient-specific estimates were obtained, thereby improving the prognostic classification, particularly for G3 patients, which could be split in further sub-groups (Table). Harrell’s C index was 0.864. Similar results were obtained for DFS.


WHO 2010 classification stratifies the risk of OS and DFS for G1 and G2 diseases. On the other hand, the risk of death for G3 disease varies according to Ki67 values, morphology and beta-catenin. Morphology has the strongest predictive power, segregating two macro groups in which beta-catenin has a lower differential effect while a prognostic gradient by Ki67 (up to Ki67 ≤55) is evident.Table:

457P Joint distribution of patients according to WHO 2010 classification by the results of the prognostic model

New Prognostic model's macro groups by Ki67 grading
WHO 2010 classificationm0,B01, Ki67 

Clinical trial identification


Legal entity responsible for the study

FONDAZIONE IRCCS Istituto Nazionale Tumori, Milano Ethical Committee Approved 48/16




All authors have declared no conflicts of interest.