title: Immunohistochemical study of the neural development transcription factors (TTF1, ASCL1 and BRN2) in neuroendocrine prostate tumours.
abstract: OBJECTIVE
  Prostatic small-cell neuroendocrine carcinoma is an uncommon malignancy that constitutes 0.5-1% of all prostate malignancies. The median cancer-specific survival of patients with prostatic small-cell neuroendocrine carcinoma is 19 months, and 60.5% of the patients have metastatic disease. Neural development transcription factors are molecules involved in the organogenesis of the central nervous system and of neuroendocrine precursors of various tissues, including the suprarenal gland, thyroid glands, lungs and prostate.
  
  
  METHODS
  We present 3 cases of this uncommon condition, applying the new World Health Organisation criteria. We conducted studies through haematoxylin and eosin staining and analysed the expression of the neural development transcription factors achaete-scute homolog like 1, thyroid transcription factor 1 and the class III/IV POU transcription factors, as a new research line in the carcinogenesis of prostatic neuroendocrine tumours.
  
  
  RESULTS
  In case 1, there was no TTF1 immunoexpression. Cases 2 and 3 had positive immunostaining for ASCL1, and Case 1 had negative immunostaining. BRN2 immunostaining was negative in case 1 and positive in cases 2 and 3.
  
  
  CONCLUSIONS
  The World Health Organisation does not recognise any molecular or genetic marker with prognostic value. ASCL-1 is related to the NOTCH and WNT signalling pathways. ASCL-1, TTF1 and BRN2 could be used for early diagnosis and as prognostic factors and therapeutic targets.
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España. Electronic address: enriquerodriguezzarco@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Zarco
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: A
authors.initials: A
authors.lastname: Vallejo-Benítez
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: S
authors.initials: S
authors.lastname: Umbría-Jiménez
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: S
authors.initials: S
authors.lastname: Pereira-Gallardo
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: S
authors.initials: S
authors.lastname: Pabón-Carrasco
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla, Santander, España.
authors.forename: A
authors.initials: A
authors.lastname: Azueta
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: R
authors.initials: R
authors.lastname: González-Cámpora
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, EE. UU.
authors.forename: P S
authors.initials: PS
authors.lastname: Espinal
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
authors.forename: A
authors.initials: A
authors.lastname: García-Escudero
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D014408:Biomarkers, Tumor; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry* / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000737:chemistry* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis*; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D050809:POU Domain Factors / Q000032:analysis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000235:genetics; D013194:Staining and Labeling; D016708:Synaptophysin / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D050809:POU Domain Factors; D016708:Synaptophysin; D014157:Transcription Factors; C065500:ASCL1 protein, human; C569014:SYP protein, human; C504003:TTF1 protein, human; C085076:transcription factor Brn-2
keywords: Achaete-scute homolog like 1; Carcinoma de célula pequeña; Cáncer de próstata; Diferenciación neuroendocrina; Factor de transcripción clase III/IV POU3F2; Factores de transcripición de desarrollo neural; Neural development transcription factors; Neuroendocrine differentiation; Prostate cancer; Small-cell carcinoma; Transcription factor class III/IV POU3F2