title: Alterations in the expression of p53, KLF4, and p21 in neuroendocrine lung tumors.
abstract: BACKGROUND
  Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis.
  
  
  OBJECTIVE
  To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors.
  
  
  METHODS
  All neuroendocrine lung neoplasms (N = 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Follow-up was assessed in all cases (119 of 119; 100%).
  
  
  RESULTS
  p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P = .04 and P = .004, respectively, Fisher exact test).
  
  
  CONCLUSIONS
  p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.
authors: From the Departments of Thoracic Surgery (Dr Naranjo Gómez) and Pathology (Drs Val Bernal, García Arranz, Lazuén Fernández, and Gómez Roman), Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors: José Manuel
authors: JM
authors: Naranjo Gómez
authors: Jose Fernando Val
authors: JF
authors: Bernal
authors: Pilar García
authors: PG
authors: Arranz
authors: Servando Lazuén
authors: SL
authors: Fernández
authors: Jose Javier Gómez
authors: JJ
authors: Roman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53