title: Neuroendocrine prostate cancer xenografts with large-cell and small-cell features derived from a single patient's tumor: morphological, immunohistochemical, and gene expression profiles.
abstract: BACKGROUND
  Small-cell carcinoma (SCC) of the prostate is an AR-negative variant of prostate cancer found at progression in 10-20% of castrate-resistant disease. Its finding predicts a distinct clinical course and a poor prognosis. Large-cell neuroendocrine carcinoma (LCNEC) is a much rarer variant that behaves similarly to SCC. The biological mechanisms that drive these disease variants are poorly understood.
  
  
  METHODS
  Eight tumor fragments from the salvage pelvic exenteration specimen of a patient with castrate-resistant prostate carcinoma were subcutaneously implanted into 6- to 8-week-old male CB17 SCID mice. Serial tissue sections and tissue microarrays of the resulting MDA PCa 144 xenograft lines were used for histopathologic and immunohistochemical characterization of the xenografts and their tissue of origin. RNA from two representative xenograft sublines was used for gene-expression profiling.
  
  
  RESULTS
  All eight fragments formed tumors: four of the MDA PCa 144 xenograft sublines had morphologic characteristics of SCC and four, of LCNEC. All retained high fidelity to their parent tumor tissue, which remained stable through serial passages. Morphological transitions in the specimen of origin suggested LCNEC represents an intermediate step between adenocarcinoma and SCC. Over 2,500 genes were differentially expressed between the SCC (MDA PCa 144-13) and the LCNEC (MDA PCa 144-4) sublines and enriched in "Nervous System Development" Gene Ontology subtree.
  
  
  CONCLUSIONS
  The eight xenograft models described represent the spectrum of neuroendocrine carcinomas in prostate cancer and will be valuable preclinical tools to study the pathogenesis of and therapy targets for this increasingly recognized subset of lethal prostate cancer.
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Ana
authors: A
authors: Aparicio
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Vasiliki
authors: V
authors: Tzelepi
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: John C
authors: JC
authors: Araujo
authors: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Charles C
authors: CC
authors: Guo
authors: Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Shoudan
authors: S
authors: Liang
authors: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Patricia
authors: P
authors: Troncoso
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Christopher J
authors: CJ
authors: Logothetis
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Nora M
authors: NM
authors: Navone
authors: Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Sankar N
authors: SN
authors: Maity
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017430:Prostate-Specific Antigen