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Prostate cancer cells that have taken on the look and the markers of nerve-and-hormone cells. A trace of it is present in almost every prostate cancer and means nothing; a tumour made mostly of it is a different and much more serious disease, and it usually appears after years of hormone treatment.
Neuroendocrine differentiation describes prostate cancer cells expressing neuroendocrine markers, principally chromogranin A, synaptophysin and CD56, with or without the morphology to match. It is a spectrum rather than a category, which is why the word appears in so many contexts with so many meanings. The Prostate Cancer Foundation working committee set out the range in a classification with six named entries: usual prostate adenocarcinoma with neuroendocrine differentiation; adenocarcinoma with Paneth cell neuroendocrine differentiation; carcinoid tumour; small cell carcinoma; large cell neuroendocrine carcinoma; and mixed neuroendocrine carcinoma with acinar adenocarcinoma, alongside two clinical descriptions, prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma, and castration-resistant prostate cancer with a small cell cancer-like clinical presentation.
The practical rule in a United Kingdom report is that scattered marker positivity in an ordinary adenocarcinoma is not looked for and does not change anything. The Royal College of Pathologists dataset does not ask for routine synaptophysin and chromogranin staining of ordinary prostate adenocarcinoma, because almost all of them show some neuroendocrine differentiation and the evidence that finding it changes treatment or prognosis is insufficient; the stains are for tumours that already look neuroendocrine down the microscope. Neuroendocrine carcinomas are not Gleason graded.
The form that matters is treatment-related. The WHO fifth edition gives treatment-related neuroendocrine prostatic carcinoma its own section in the prostate chapter rather than folding it into the classification's neuroendocrine chapter, and defines it as tumours demonstrating complete neuroendocrine differentiation, or partial neuroendocrine differentiation with adenocarcinoma, following androgen deprivation therapy, covering both the primary and its metastases. It is found in 10.5 to 17 percent of people with metastatic castration-resistant prostate cancer treated with androgen receptor signalling inhibitors, and the evidence is that it arises by transformation of an existing adenocarcinoma rather than from resident neuroendocrine cells, which is what lineage plasticity means in this disease. PSA and NKX3.1 are usually lost, which is why the blood test can stay reassuringly low while the disease advances, and why an unexplained clinical deterioration with a flat prostate-specific antigen is the situation in which a biopsy is worth taking.
In plain words · TP53 is the 'guardian of the genome', broken in half of all cancers. Fixing it directly has so far defeated every attempt, so drugs exploit what its loss makes cancers depend on.
Showing the target this term concerns: TP53.
Biopsy of progressing lesions, especially with low PSA or visceral spread, is recommended to detect neuroendocrine transformation and switch to platinum-based therapy or trials.
A mechanism for the most feared form of treatment resistance in prostate cancer, and the reason combined TP53 and RB1 loss is worth knowing about before a man starts an androgen receptor drug rather than after his biopsy comes back neuroendocrine. Reversibility in the laboratory is also an argument that the switch is a target and not just a prognosis.
Treatment-emergent neuroendocrine prostate cancer is understood as lineage plasticity under androgen receptor blockade; EZH2, DLL3 and Aurora kinase are the targets under investigation.
The first predictive resistance biomarker in prostate cancer, and a mechanism rather than a correlation: a receptor with no ligand-binding domain cannot be blocked by a drug that binds the ligand-binding domain. It is also the origin of the case for androgen receptor degraders, which destroy the protein rather than blocking a site the protein no longer has.
Shares AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer, Neuroendocrine and small-cell prostate cancer, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC) and the tags gu, prostate-glossary.
Shares AR-V7 splice variant, Castration-resistant prostate cancer (CRPC), Androgen receptor, Acquired resistance to every therapy and the tags gu, prostate-glossary.
Shares AR-V7 splice variant, Acquired resistance to every therapy, TP53, Metastatic castration-resistant prostate cancer and the tags gu, prostate-glossary.
Shares Tumour heterogeneity and clonal evolution, Metastatic castration-resistant prostate cancer, Prostate cancer and the tags gu, prostate-glossary.
Shares Gleason score / Grade Group, PSA (prostate-specific antigen), Prostate cancer and the tags gu, prostate-glossary.
Shares Gleason score / Grade Group, PSA (prostate-specific antigen), Prostate cancer and the tags gu, prostate-glossary.
Shares PSA (prostate-specific antigen), Androgen receptor, Prostate cancer and the tags gu, prostate-glossary.
Shares Gleason score / Grade Group, Prostate cancer and the tags gu, prostate-glossary.