title: Differential expression of forkhead box M1 and its downstream cyclin-dependent kinase inhibitors p27(kip1)  and p21(waf1/cip1)  in the diagnosis of pulmonary neuroendocrine tumours.
abstract: OBJECTIVE
  Pulmonary neuroendocrine (NE) tumours represent a spectrum of phenotypically distinct entities with different biological behaviours. Difficulties in classifying these tumours are frequently encountered in clinical practice. Forkhead box M1 (FoxM1) is essential for the development of various cancers and is a proliferation-specific transcription factor that regulates transcription of cell cycle genes, including cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1) . This study was performed to determine the utility of FoxM1, p27(kip1) and p21(waf1/cip1) as immunomarkers for subtyping pulmonary NE tumours.
  
  
  RESULTS
  FoxM1, p27(kip1) and p21(waf1/cip1) expression was evaluated by immunohistochemistry in 60 pulmonary NE tumours [19 typical carcinoids (TCs), six atypical carcinoids (ACs), 17 large cell neuroendocrine carcinomas (LCNECs) and 18 small cell lung cancers (SCLCs)]. The frequencies of FoxM1 and p21(waf1/cip1) expression were significantly different between TCs and ACs (each P = 0.009), and those of FoxM1 and p27(kip1) expression were significantly different between LCNECs and SCLCs (P = 0.012 and P = 0.002, respectively). The combined FoxM1((-)) /p21(waf1/cip1(-)) and FoxM1((+)) /p27(kip1(high)) phenotypes had the best diagnostic accuracy for distinguishing TCs from ACs, and SCLCs from LCNECs, respectively.
  
  
  CONCLUSIONS
  FoxM1, p27(kip1) and p21(waf1/cip1) showed distinct immunoreactivity according to histological subtype, which may be of value as an ancillary test in the differential diagnosis of pulmonary NE tumours.
authors.affiliation: Department of Pathology, Gachon University of Medicine and Science, Incheon, South Korea.
authors.forename: Seung Yeon
authors.initials: SY
authors.lastname: Ha
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Chang
authors.forename: Sunhee
authors.initials: S
authors.lastname: Chang
authors.forename: Kun Young
authors.initials: KY
authors.lastname: Kwon
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Mee Sook
authors.initials: MS
authors.lastname: Roh
authors.forename: Boram
authors.initials: B
authors.lastname: Seo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27