title: The oncofetal protein IMP3: a useful marker to predict poor clinical outcome in neuroendocrine tumors of the lung.
abstract: BACKGROUND
  We evaluated the expression of the oncofetal protein IMP3 in a series of neuroendocrine tumors of the lung, correlating our results with proliferating index Ki67 and with the expression of the two most studied stem cell markers in lung cancer, Nanog and Oct3/4.
  
  
  METHODS
  A total of 74 patients with a diagnosis of neuroendocrine tumor including 46 cases of typical carcinoid, nine cases of atypical carcinoids, 13 cases of large cell neuroendocrine carcinomas and six cases of small cell carcinomas were enrolled.
  
  
  RESULTS
  IMP3 was expressed in 50% of small cell carcinomas, 84% of large cell neuroendocrine carcinomas, 55% of atypical carcinoids and 10% of typical carcinoids. IMP3-positive cases showed significantly decreased overall and disease-free survival time compared with IMP3-negative cases. Nanog was expressed in 50% of small cell carcinomas, 31% of large cell neuroendocrine carcinomas, 33% of atypical carcinoids and 15% of typical carcinoids, and 68% of IMP3-positive tumors were also enriched for Nanog expression. Conversely, Oct3/4 expression could not be detected in all the analyzed series. When combining Ki67 and IMP3 expression we demonstrated that all the cases with a Ki67 index higher than 4% were also IMP3-positive, and their simultaneous expression was a poor prognostic factor.
  
  
  CONCLUSIONS
  IMP3 is a marker of poor outcome in lung neuroendocrine tumors; its correlation with Nanog expression suggest an implication of IMP3 in stem cell processes and its association with a Ki67 labeling index higher than 4% stratifies a subset of atypical carcinoids with a higher risk of recurrence and mortality.
authors.affiliation: *Division of Pathology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; †Department of Pathophysiology and Organ Transplant, University of Milan, Milan, Italy; ‡Division of Thoracic Surgery, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy; §Division of Pathology, Department of Health Sciences, University of Milan and A.O. San Paolo, Milan, Italy; and ‖Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Del Gobbo
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaira
authors.forename: Elena
authors.initials: E
authors.lastname: Guerini Rocco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palleschi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bulfamante
authors.forename: Dario
authors.initials: D
authors.lastname: Ricca
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiori
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
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*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins