title: Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma.
abstract: OBJECTIVE
  Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor.
  
  
  METHODS
  We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin-fixed paraffin-embedded specimens.
  
  
  RESULTS
  We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in 63% of small cell carcinomas (17 of 27), with 38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation.
  
  
  CONCLUSIONS
  Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.
authors: Authors' Affiliations: Pathology, Department of Pathology, Henry Ford Health System, Detroit, Michigan; Oncology, and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors: Hsueh-Li
authors: HL
authors: Tan
authors: Akshay
authors: A
authors: Sood
authors: Hameed A
authors: HA
authors: Rahimi
authors: Wenle
authors: W
authors: Wang
authors: Nilesh
authors: N
authors: Gupta
authors: Jessica
authors: J
authors: Hicks
authors: Stacy
authors: S
authors: Mosier
authors: Christopher D
authors: CD
authors: Gocke
authors: Jonathan I
authors: JI
authors: Epstein
authors: George J
authors: GJ
authors: Netto
authors: Wennuan
authors: W
authors: Liu
authors: William B
authors: WB
authors: Isaacs
authors: Angelo M
authors: AM
authors: De Marzo
authors: Tamara L
authors: TL
authors: Lotan
mesh_terms: D018267:Carcinoma, Acinar Cell / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human