# Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer

Source: https://onco.cc/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/  
OnCo record `paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Among 150 men tested regardless of family history, the ones with an inherited repair fault were four times as likely to have a particular growth pattern on their pathology report.

## Summary

One hundred and fifty consecutive unselected patients with recurrent or metastatic prostate cancer were offered germline genetic testing by a single oncologist using a clinical-grade 30-gene saliva assay. Pathogenic mutations were identified in 21 men, 14%: 9 in BRCA2, 3 in ATM, 3 in CHEK2 and 2 in BRCA1. There were no associations between germline mutation and age, tumour stage, Gleason sum or family history. Mutation-positive men had lower median PSA at diagnosis, 5.5 against 8.6 ng/mL, and distinctive pathological features: intraductal or ductal histology in 48% against 12%, and lymphovascular invasion in 52% against 14%. Forty-four per cent of the men with a positive germline test would not have been offered genetic screening under the National Comprehensive Cancer Network guidelines then in force.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: The Prostate
- Year: 2018
- DOI: 10.1002/pros.23484
- Authors: Isaacsson Velho P, Silberstein JL, Markowski MC, et al.
- Findings: Pathogenic germline mutations in 21 of 150 men, 14%; BRCA2 in 9, ATM in 3, CHEK2 in 3, BRCA1 in 2.; Intraductal or ductal histology in 48% of carriers against 12% of non-carriers.; Lymphovascular invasion in 52% against 14%.; No association with age, stage, Gleason sum or family history; 44% of carriers would not have qualified for testing.
- What it means: It links a line on a UK pathology report to a question about a family. Intraductal carcinoma is a reportable item in the current dataset, and its presence is a practical prompt to check that germline testing has actually been offered rather than assumed.
- Caveats: One hundred and fifty consecutive patients of a single oncologist, so referral patterns shape it.; Retrospective pathology review.; Neither finding is sensitive enough to select who is tested; the case for unselected testing stands.

## Sources

- Isaacsson Velho et al., The Prostate 2018: intraductal or ductal histology and lymphovascular invasion associated with germline DNA-repair gene mutations in 150 consecutively tested men: https://doi.org/10.1002/pros.23484
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29368341/

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [CHEK2](https://onco.cc/targets/chek2/)
- pathways: [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/)
- terms: [Cribriform growth pattern in prostate cancer](https://onco.cc/terms/cribriform-prostate-cancer/), [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Intraductal carcinoma of the prostate (IDC-P)](https://onco.cc/terms/intraductal-carcinoma-prostate/)
- biomarkers: [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/)

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