title: Clinicopathological and molecular genetic analysis of 4 typical Chinese HNPCC families.
abstract: OBJECTIVE
  To study the clinicopathological and molecular genetic characteristics of typical Chinese hereditary nonpolyposis cotorectal cancer (HNPCC) families.
  
  
  METHODS
  Four typical Chinese HNPCC families were analyzed using microdissection, microsatellite instability analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes.
  
  
  RESULTS
  All five tumor tissues of 4 probands from the 4 typical Chinese HNPCC families showed microsatellite instability at more than two loci (MSI-H or RER+ phenotype). Three out of the 4 cases lost hMSH2 protein expression and the other case showed no hMLH1 protein expression. Three pathological germline mutations (2 in hMSH2 and 1 in hMLH1), which had not been reported previously, were identified. The same mutations were also found in other affected members of two HNPCC families,respectively.
  
  
  CONCLUSIONS
  Typical Chinese HNPCC families showed relatively frequent germline mutation of mismatch repair genes. High-level microsatellite instability and loss of expression of mismatch repair genes correlated closely with germline mutation of mismatch repair genes. Microsatellite instability analysis and immunostaining of mismatch repair gene might serve as effective screening methods before direct DNA sequencing. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC families.
authors.affiliation: Department of Pathology, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Cai
authors.forename: M H
authors.initials: MH
authors.lastname: Sun
authors.forename: H F
authors.initials: HF
authors.lastname: Lu
authors.forename: T M
authors.initials: TM
authors.lastname: Zhang
authors.forename: S J
authors.initials: SJ
authors.lastname: Mo
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: S J
authors.initials: SJ
authors.lastname: Cai
authors.forename: X Z
authors.initials: XZ
authors.lastname: Zhu
authors.forename: D R
authors.initials: DR
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D002681:China; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D010375:Pedigree