1. Neuroendocrine differentiation in usual‐type prostatic adenocarcinoma: Molecular characterization and clinical significance
- Author
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Iryna Samarska, Jonathan I. Epstein, Tamara L. Lotan, Harsimar B. Kaur, Mohamed Alshalalfa, Edward M. Schaeffer, Sanjana Murali, Jiayun Lu, Benjamin L. Maughan, Emmanuel S. Antonarakis, Corinne E. Joshu, Juan Miguel Mosquera, Farzana A. Faisal, and Kaushal Asrani
- Subjects
Male ,0301 basic medicine ,Ubiquitin-Protein Ligases ,Urology ,Adenocarcinoma ,Neuroendocrine differentiation ,Article ,Metastasis ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Neuroendocrine Cells ,medicine ,Carcinoma ,Humans ,Enzalutamide ,PTEN ,Carcinoma, Small Cell ,Retrospective Studies ,biology ,business.industry ,PTEN Phosphohydrolase ,Prostatic Neoplasms ,Chromogranin A ,Cell Differentiation ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Neuroendocrine Tumors ,Prostatic Neoplasms, Castration-Resistant ,Retinoblastoma Binding Proteins ,030104 developmental biology ,Oncology ,chemistry ,Receptors, Androgen ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Tumor Suppressor Protein p53 ,business ,Signal Transduction - Abstract
BACKGROUND Small cell neuroendocrine (NE) carcinomas of the prostate classically lose androgen receptor (AR) expression, may harbor loss of the RB1, TP53, and PTEN tumor suppressor genes, and are associated with a poor prognosis. However usual-type adenocarcinomas may also contain areas of NE differentiation, and in this context the molecular features and biological significance are less certain. METHODS We examined the molecular phenotype and oncologic outcomes of primary prostate adenocarcinomas with ≥5% NE differentiation (≥5% chromogranin A-positive NE cells in any given tumor spot on tissue microarray) using three independent study sets: a set of tumors with paneth cell-like NE differentiation (n = 26), a retrospective case-cohort of intermediate- and high-risk patients enriched for adverse outcomes (n = 267), and primary tumors from a retrospective series of men with eventual castration-resistant metastatic prostate cancer (CRPC) treated with abiraterone or enzalutamide (n = 55). RESULTS Benign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P
- Published
- 2020