ArticleThe Prostate2020
Neuroendocrine differentiation in usual-type prostatic adenocarcinoma: Molecular characterization and clinical significance.
Article in The Prostate, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Clinicopathologic and molecular characteristics of neuroendocrine carcinomas of the gallbladder.Histology and histopathology · 2025Article
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- Large Cell Neuroendocrine Prostate Cancer: Large Is Not Small.The oncologist · 2024Article
- Plasma progastrin-releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis-targeted agents in patients with metastatic castration-resistant prostate cancer.Cancer reports (Hoboken, N.J.) · 2023Article
- Neuroendocrine differentiation in the setting of prostatic carcinoma: contemporary assessment of a consecutive series.Histopathology · 2022Article
- Review
- Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.Journal of experimental & clinical cancer research : CR · 2022Review
- LncRNA EIF3J-AS1 functions as an oncogene by regulating MAFG to promote prostate cancer progression.Journal of Cancer · 2022Article
- Delineating the Molecular Events Underlying Development of Prostate Cancer Variants with Neuroendocrine/Small Cell Carcinoma Characteristics.International journal of molecular sciences · 2021Review
- [Localized prostate cancer].Der Pathologe · 2021Article
- A novel liquid biopsy (NETest) identifies paragangliomas and pheochromocytomas with high accuracy.Endocrine-related cancer · 2021Article
- A first case of ductal adenocarcinoma of the prostate having characteristics of neuroendocrine phenotype with PTEN, RB1 and TP53 alterations.BMC medical genomics · 2021Article
- Preclinical Models in Prostate Cancer: Resistance to AR Targeting Therapies in Prostate Cancer.Cancers · 2021Review
- Clinical and Biological Features of Neuroendocrine Prostate Cancer.Current oncology reports · 2021Review
- Experience and Lessons Learned in the Treatment of Transforming Small Cell Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review.Case reports in oncologyArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundSmall 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.
methodsWe 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).
resultsBenign NE cells expressed significantly lower quantified AR levels compared with paired benign luminal cells (P < .001). Similarly, paneth-like NE carcinoma cells or carcinoma cells expressing chromogranin A expressed significantly lower quantified AR levels than paired non-NE carcinoma cells (P < .001). Quantified ERG protein expression, was also lower in chromogranin A-labeled adenocarcinoma cells compared with unlabeled cells (P < .001) and tumors with NE differentiation showed lower gene expression scores for AR activity compared with those without. Despite evidence of lower AR signaling, adenocarcinomas with NE differentiation did not differ by prevalence of TP53 missense mutations, or PTEN or RB1 loss, compared with those without NE differentiation. Finally, NE differentiation was not associated with time to metastasis in intermediate- and high-risk patients (P = .6 on multivariate analysis), nor with progression-free survival in patients with CRPC treated with abiraterone or enzalutamide (P = .9).
conclusionNE differentiation in usual-type primary prostate adenocarcinoma is a molecularly and clinically distinct form of lineage plasticity from that occurring in small cell NE carcinoma.
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