{"entity":{"id":"paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018","kind":"paper","name":"Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer","aka":[],"tldr":"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.","asOf":"2026-09-25","links":[{"label":"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","url":"https://doi.org/10.1002/pros.23484"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29368341/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["germline-testing","histopathology-ihc"],"targets":["brca","atm","chek2"],"drugs":[],"companies":[],"institutions":[],"pathways":["homologous-recombination-repair","ddr"],"terms":["germline-vs-somatic","gbrca-mutation","hrd","intraductal-carcinoma-prostate","cribriform-prostate-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"The Prostate","year":2018,"doi":"10.1002/pros.23484","pmid":"29368341","authors":"Isaacsson Velho P, Silberstein JL, Markowski MC, et al.","paperType":"observational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":150},"route":"/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"atm","kind":"target","name":"ATM","route":"/targets/atm/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"chek2","kind":"target","name":"CHEK2","route":"/targets/chek2/"}],"pathway":[{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"}],"term":[{"id":"cribriform-prostate-cancer","kind":"term","name":"Cribriform growth pattern in prostate cancer","route":"/terms/cribriform-prostate-cancer/"},{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"intraductal-carcinoma-prostate","kind":"term","name":"Intraductal carcinoma of the prostate (IDC-P)","route":"/terms/intraductal-carcinoma-prostate/"}],"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"}]}}