Document Detail

High grade prostatic intraepithelial neoplasia does not display loss of heterozygosity at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer.
MedLine Citation:
PMID:  23035815     Owner:  NLM     Status:  Publisher    
What's known on the subject? and What does the study add? The risk of developing aggressive prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. An earlier study by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer showed that BRCA2 mutation carriers displayed a loss of heterozygosity (LOH) within their prostate cancer tissue in the majority of cases, thus implying that the prostate cancer in these men occurred as a result of LOH for BRCA2. High grade prostatic intraepithelial neoplasia (HGPIN) has been considered a precursor to prostate adenocarcinoma in some, but not all, cases of prostate adenocarcinoma. The study found that there was no LOH for BRCA2 in HGPIN. From this small cohort of BRCA2-positive men, we suggest HGPIN is not necessarily a precursor to their prostate cancer development. The presence of HGPIN in a TRUS biopsy in these men at risk of high risk disease is not an indication for prostatectomy. OBJECTIVES: •  To determine if high grade prostatic intraepithelial neoplasia (HGPIN), which is considered a precursor to the development of prostate adenocarcinoma, displays the same genetic hallmarks as adenocarcinoma. •  To identify, using molecular genetic techniques, if HGPIN is a precursor of tumour development and progression in men carrying a pathogenic germline mutation in BRCA2. PATIENTS AND METHODS: •  Ten participants from the Kathleen Cuningham Consortium for Research into Familial Breast Cancer cohort of high-risk breast cancer families were identified, with (i) a diagnosis of aggressive prostate cancer and presence of HGPIN, (ii) a pathogenic BRCA2 mutation, and (iii) access to archival prostate tissue specimens. •  Loss of heterozygosity (LOH) at the BRCA2 gene was examined using mutation-specific PCR and sequencing of DNA from laser microdissected HGPIN. RESULTS: •  Within this cohort of 10 pathogenic BRCA2 carriers, no patient displayed LOH at the mutation locus within HGPIN, irrespective of whether or not corresponding adenocarcinoma DNA displayed LOH. CONCLUSIONS: •  Although HGPIN is considered a precursor to cancer, as no LOH was observed, this assay does not provide a genetic marker that may be considered a positive predictor of tumorigenesis in BRCA2 carriers. •  In this group of high-risk men, early screening via prostate-specific antigen testing, rectal examination and prostate biopsy may be prudent to permit the detection and the optimum clinical management of prostate cancer.
Amber Willems-Jones; Liam Kavanagh; David Clouston; Damien Bolton; ; Stephen Fox; Heather Thorne
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  BJU international     Volume:  -     ISSN:  1464-410X     ISO Abbreviation:  BJU Int.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100886721     Medline TA:  BJU Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab), Research Department, Peter MacCallum Cancer Centre, East Melbourne Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville Department of Urology, Austin Hospital, Heidelberg Focus Pathology, South Yarra Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
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