Neuroendocrine prostate cancer xenografts with large-cell and small-cell features derived from a single patient's tumor: Morphological, immunohistochemical, and gene expression profiles

• Published in: The Prostate Vol. 71; no. 8; pp. 846 - 856
• Main Authors: Aparicio, Ana, Tzelepi, Vasiliki, Araujo, John C., Guo, Charles C., Liang, Shoudan, Troncoso, Patricia, Logothetis, Christopher J., Navone, Nora M., Maity, Sankar N.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2011; Wiley-Liss
• Subjects: Aged; androgen-independent; Animals; Antineoplastic Agents - therapeutic use; array; Biological and medical sciences; cancer; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - pathology; Carcinoma, Large Cell - radiotherapy; Carcinoma, Neuroendocrine - drug therapy; Carcinoma, Neuroendocrine - pathology; Carcinoma, Neuroendocrine - radiotherapy; Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - pathology; Carcinoma, Small Cell - radiotherapy; castrate-resistant; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Mice; Mice, SCID; Nephrology. Urinary tract diseases; neural development; Prostate-Specific Antigen; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Xenograft Model Antitumor Assays; Immunohistochemistry; Andrology; Nephrology; Prostate disease; Nervous system; Transplantation; Heterograft; Heterotransplantation; array; Surgery; Hormonoindependence; Development; Graft; Male genital diseases; Tumor cell; androgen-independent; Human; Urinary system disease; Androgen; Gynecology; Malignant tumor; neural development; Gene expression profile; Resistance; Anatomic pathology; Treatment; castrate-resistant; Animal; Morphology; Sex steroid hormone; Prostate cancer; Cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21301

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. CONCLUSION 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. Prostate 71:846–856, 2011. © 2010 Wiley‐Liss, Inc.