title: IMP3 expression in small-intestine neuroendocrine neoplasms: a new predictor of recurrence.
abstract: OBJECTIVE
  Small-intestine neuroendocrine neoplasms are heterogeneous neoplasms arising from endocrine cells of the intestinal mucosa. Ki-67 is the main determinant of prognosis in neuroendocrine neoplasms. However, the search for new prognostic makers represents a key point with regard to small-intestine neuroendocrine neoplasms. The oncofetal protein IMP3 plays a role in cell growth and its expression has a prognostic value in lung neoplasms.
  
  
  METHODS
  From January 1998 to August 2015, all the consecutive small-intestine neuroendocrine neoplasms patients suitable for surgery were included: 51 patients (32 males, median age 68 years) had small-intestine neuroendocrine neoplasms classified according to the WHO 2010 classification. In all the cases IMP3 expression was evaluated on primary tumors and, when available, on nodal and distant metastases. The medical records and pathological slides of these patients were used to determine the clinical characteristics, pathological diagnoses, and outcome information.
  
  
  RESULTS
  The overall 5-year and 10-year survival rate were 53.9 and 42% respectively. At Cox proportional hazards regression grading was the major factor influencing both OS and progression-free survival at univariate (p = 0.0002 and 0.0051, respectively) and multivariate analysis (p = 0.0004 and 0.0043, respectively). Also IMP3 expression at the nodal metastases resulted a factor significantly associated with progression-free survival at both univariate (p = 0.0066) and multivariate analysis (p = 0.0059, HR 3.58). IMP3 expression did not correlate with the Ki-67 (p = n.s.).
  
  
  CONCLUSIONS
  In this study, IMP3 at the nodal site resulted to be associated with low progression-free survival in small-intestine neuroendocrine neoplasms, independently of the Ki-67 index. We suggest that the integration of IMP3 and Ki-67 would help better stratify the risk of progression in small-intestine neuroendocrine neoplasms.
authors.affiliation: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, Italy. sara.massironi@policlinico.mi.it.
authors.forename: Sara
authors.identifier: http://orcid.org/0000-0003-3214-8192
authors.initials: S
authors.lastname: Massironi
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Del Gobbo
authors.affiliation: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavalcoli
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiori
authors.affiliation: Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, Italy.|Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Conte
authors.affiliation: Anatomic Pathology 1, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Pellegrinelli
authors.affiliation: Anatomic Pathology 1, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Milione
authors.affiliation: Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.|Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins
keywords: IMP3 expression; Nodal metastasis; Prognostic makers; Small-intestine neuroendocrine neoplasms