title: Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung.
abstract: BACKGROUND
  Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated their expression in 96 NELT and correlated it to clinical features including survival.
  
  
  METHODS
  Paraffin embedded material from 50 typical carcinoids (TC), 13 atypical carcinoids (AC), 23 large cell neuroendocrine carcinomas (LCNEC) and 10 small cell lung carcinomas (SCLC) was evaluated by immunohistochemisty.
  
  
  RESULTS
  Significantly higher expression of EZH2 was found in high grade NELT (LCNEC + SCLC) versus low grade NELT (TC + AC) (p < 0.0001). High expression of BMI1 was observed in low grade NELT (TC + AC) in contrast to the expression in high grade NELT (LCNEC+SCLC) (p=0.004). In multivariate models, diagnosis was the strongest predictor of survival.
  
  
  CONCLUSIONS
  The immunohistochemical expression of EZH2 and BMI1 are significantly different in low versus high grade NELT. This difference might be related to NELT tumorigenesis. These markers have no independent prognostic impact in NELT. Whether EZH2 could become target in new treatments strategies against NELT remains to be elucidated.
authors.affiliation: Department of Radiation Biology, Finsen Center, Copenhagen University Hospital, Copenhagen, Denmark. anloudk@yahoo.com
authors.forename: Anna-Louise Reinert Ørsum
authors.initials: AL
authors.lastname: Bondgaard
authors.forename: Thomas Tuxen
authors.initials: TT
authors.lastname: Poulsen
authors.forename: Hans Skovgaard
authors.initials: HS
authors.lastname: Poulsen
authors.forename: Birgit Guldhammer
authors.initials: BG
authors.lastname: Skov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis*; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C069077:BMI1 protein, human; D019394:Ki-67 Antigen; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1