title: [Clinical analysis and molecular genetic study of hereditary nonpolyposis colorectal cancer kindreds].
abstract: OBJECTIVE
  To study the clinicopathological and molecular genetic characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), to enable the early diagnosis and to evaluate the treatment.
  
  
  METHODS
  We analyzed 12 families of HNPCC from Wenzhou, Zhejiang province, China. Mismatch repair genes hMSH2 and hMLH1 expression and microsatellite instability of tumor tissue were studied using microdissection, microsatellite analysis, immunohistochemical staining and Gene Scan analysis. Direct DNA sequencing of hMSH2 and hMLH1 were performed subsequently.
  
  
  RESULTS
  Altogether 32 patients with colorectal cancer were recognized in 12 HNPCC families, with the median age of 45.2 years (75.0% before the age of 50 years). The proximal tumors accounted for 51.1%, while multiple colorectal cancers accounted for 34.4%. Poor differentiation cancers occupied half of the patients (53.1%). And 68.8% of the patients had the tumor of Dukes A and B. Among 12 HNPCC families, 7 cases in 6 HNPCC families developed extracolonic cancer. 13 cases died during follow up of 1 - 23 years. The median survival time was 6.4 years. 19 alive cases followed up from 1 to 28 years. All tumors (9/9) displayed microsatellite instability, with the half losing hMSH2 or hMLH1 expression. In the 5 genetic analyzed kindreds 3 possessed germline mutation. Two of three mutations have not been reported in the worldwide database previously.
  
  
  CONCLUSIONS
  HNPCC showed distinct clinicopathological characteristics. Microsatellite instability analysis and immunohistochemical staining might be the effective screening methods before direct DNA sequencing for the detection of mutation in mismatch repair genes. It is important to analyze the members of affected families.
authors.affiliation: Department of Surgical Oncology, Second Peoples' Hospital of Wenzhou, Wenzhou 325028, China.
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: Chong-wei
authors.initials: CW
authors.lastname: Tao
authors.forename: Zhe-jing
authors.initials: ZJ
authors.lastname: Chen
authors.forename: Da-ren
authors.initials: DR
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D002681:China; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; 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