[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Lower urinary tract and male genital system](https://durgical.com/en/general-pathology/areas/urinary-male/) › Prostate cancer: pathogenesis # Prostate cancer: pathogenesis - Mechanism Prostate cancer grows on androgens and builds on inherited risk, gene fusions and loss of tumour suppressors. Updated Nov 12, 2026 ## Key points - Risk factors: age, African ancestry, family history, germline BRCA2 and HOXB13 variants. - Androgen dependence: no cancer in men castrated before puberty; androgen deprivation shrinks tumours. - TMPRSS2-ERG fusion: androgen-driven expression of an ETS oncogene, in about half of cases. - PTEN loss and PI3K activation; TP53 and RB loss in advanced or neuroendocrine disease. - High-grade PIN: atypical cells in pre-existing glands with an intact basal layer; often next to carcinoma. ## What it is Prostatic adenocarcinoma is the commonest cancer of men in many countries and one of the leading causes of cancer death in men, including in Colombia. Its risk rises with age, with African ancestry and with family history. Androgens are needed for growth: the tumour depends on the androgen receptor, which is why androgen deprivation works and why resistance often involves receptor amplification or variants. Germline variants in BRCA2, BRCA1, ATM, HOXB13 and mismatch repair genes raise risk. About half of tumours carry fusions of the androgen-regulated TMPRSS2 gene to ETS transcription factors (ERG); PTEN loss activates PI3K-AKT signalling. High-grade prostatic intraepithelial neoplasia (PIN) is the precursor. ## Step by step - Inherited variants and age-related damage accumulate in luminal cells of the peripheral zone. - Atypical cells fill existing ducts and acini: high-grade PIN. - Androgen-receptor signalling drives a TMPRSS2-ERG fusion or other ETS rearrangement. - PTEN loss and NKX3-1 loss promote growth and invasion; the basal layer disappears. - Androgen deprivation shrinks the tumour, but clones that amplify or alter the androgen receptor escape. - Castration-resistant clones metastasize, mainly to bone. ## Clinical notes - Men with BRCA2 variants have earlier and more aggressive prostate cancer and may benefit from PARP inhibitors. - Screening with PSA is a shared decision because many detected cancers would never cause harm. ## Memory aid Old age, androgen fuel and a fused ERG: the three ingredients of prostate cancer. ## Test yourself Think of the answer, then tap the question to see it. ## What is the most common gene fusion in prostate cancer? TMPRSS2-ERG, which puts an ETS transcription factor under androgen control. ## Which inherited gene variant most clearly raises the risk of aggressive prostate cancer? BRCA2 (HOXB13 also increases risk). ## What distinguishes high-grade PIN from invasive carcinoma? In PIN the atypical cells stay within pre-existing glands that keep their basal cell layer. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/prostate-cancer-pathogenesis/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Translocations, amplifications and epigenetic changes in cancer](https://durgical.com/en/general-pathology/translocations-amplifications-and-epigenetic-changes-in-cancer/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Nuclear receptors](https://durgical.com/en/biochemistry/topics/nuclear-receptors/) ## Connections ## Related 5 - [Prostatic adenocarcinoma: Gleason and grade groups](https://durgical.com/en/general-pathology/prostatic-adenocarcinoma-gleason-and-grade-groups/) - [Benign prostatic hyperplasia](https://durgical.com/en/general-pathology/benign-prostatic-hyperplasia/) - [Translocations, amplifications and epigenetic changes in cancer](https://durgical.com/en/general-pathology/translocations-amplifications-and-epigenetic-changes-in-cancer/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Dysplasia and carcinoma in situ](https://durgical.com/en/general-pathology/dysplasia-and-carcinoma-in-situ/) ## Related conditions 3 - [Prostate cancer](https://durgical.com/en/conditions/prostate-cancer/) - [Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) - [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Prostate Cancer](https://www.ncbi.nlm.nih.gov/books/NBK470550/) (StatPearls (NCBI Bookshelf), 2024). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/prostate-cancer-pathogenesis/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/prostate-cancer-pathogenesis/