Hereditary prostate cancer as a feature of Lynch syndrome.

Published

Journal Article

Lynch Syndrome is an autosomal dominant condition characterized by early onset colorectal cancer (CRC) and is associated with cancers of the gastrointestinal and reproductive tracts. Germline mutations in DNA mismatch repair (MMR) genes have been causally associated with cancers of Lynch Syndrome. We investigated the occurrence of prostate cancer (PCa) in families with a history of colorectal cancer to assess prostate cancer as a feature of the Lynch Syndrome spectrum. Family pedigrees containing at least one CRC case as well as those meeting guidelines for Lynch Syndrome were identified and tumors were requested from participants who underwent radical prostatectomy (RP). Selected families were analyzed for association with type of PCa and clinical characteristics of aggressive disease. Microsatellite Instability (MSI) analysis was preformed on available tumors and correlated to loss of expression in MMR genes by immunohistochemical (IHC) staining. 95 individuals were identified as members of potential Lynch Syndrome families who underwent RP and 35 tumors from 31 families were received for MSI analysis. Two tumors from two unrelated families with known MMR mutations were MSI-high and one additional case from a third family was MSI-low. The remainder of the prostate cancer cases demonstrated no evidence of MSI. PCa incidence in families enriched for hereditary PCa with a history of Lynch Syndrome cancers is not strongly suggestive of the presence of an MMR mutation. However prostate tumors in known MMR mutation carriers did display MSI and loss of gene expression suggesting that PCa may arise in Lynch Syndrome due to defective DNA mismatch repair.

Full Text

Duke Authors

Cited Authors

  • Bauer, CM; Ray, AM; Halstead-Nussloch, BA; Dekker, RG; Raymond, VM; Gruber, SB; Cooney, KA

Published Date

  • March 2011

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 37 - 42

PubMed ID

  • 20872076

Pubmed Central ID

  • 20872076

Electronic International Standard Serial Number (EISSN)

  • 1573-7292

Digital Object Identifier (DOI)

  • 10.1007/s10689-010-9388-8

Language

  • eng

Conference Location

  • Netherlands