title: Clinicopathological and molecular genetic analysis of HNPCC in China.
abstract: OBJECTIVE
  To explore the clinicopathological and molecular genetic features of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population.
  
  
  METHODS
  We collected 16 Chinese HNPCC families from Wenzhou, Zhejiang Province, China. Tumor tissues and peripheral white blood cells were studied using microdissection, microsatellite analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes.
  
  
  RESULTS
  (1) A total of 50 patients had CRC. Average age at diagnosis of the first CRC was 45.7 years; 40.9% and 28.7% of the CRCs were located proximal to the splenic flexure and in the rectum, respectively. Thirty-eight percent of the colorectal cancer patients had synchronous and metachronous CRC. 34.4% and 25% of the CRCs were poor differentiation cancer and mucinous adenocarcinoma, respectively. Fourteen extracoloni tumors were found, and the hepatic cancer was the most common tumor type. Twenty-one patients whose median survival time was 5.7 years died during 1-23 years. Twenty-nine patients have survived for 1-28 years, 58.6%, 41.4% and 24.1% patients have survived for more than 5, 10 and 15 years, respectively; (2) All nine tumor-tissues showed microsatellite instability (MSI) at more than two loci. Four tumor-tissues lost hMSH2 protein expression and one lost hMLH1 protein expression. Three pathological germline mutations were identified from five genetically analyzed families; two of three mutations had not been reported previously as they were a transition from C to A in exon 14 (codon 743) of hMSH2 and a TTC deletion in exon 14 (codon 530) of hMLH1.
  
  
  CONCLUSIONS
  Chinese HNPCC have specific clinicopathological features, such as early onset, propensity to involve the proximal colon, and high frequency of multiple CRCs, liver cancer more frequent than endometrial cancer. Chinese HNPCC showed relatively frequent germline mutation of mismatch repair (MMR) genes that correlated closely with high-level MSI and loss of expression of MMR genes protein.
authors.affiliation: Department of Surgical Oncology, Second People's Hospital of Wenzhou, Wenzhou 325028, Zhejiang Province, China. luodingcun@mail.wzptt.zj.cn
authors.forename: Ding-Cun
authors.initials: DC
authors.lastname: Luo
authors.forename: Qi
authors.initials: Q
authors.lastname: Cai
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Ni
authors.forename: Shi-Chang
authors.initials: SC
authors.lastname: Ni
authors.forename: Zhe-Jing
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Li
authors.forename: Chong-Wei
authors.initials: CW
authors.lastname: Tao
authors.forename: Xue-Miao
authors.initials: XM
authors.lastname: Zhang
authors.forename: Da-Ren
authors.initials: DR
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins; D002681:China; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein