title: Microsatellite instability and hMLH1 and hMSH2 gene expression in Taiwanese hereditary nonpolyposis colorectal cancer.
abstract: OBJECTIVE
  The mutation rate of hMSH2 and hMLH1 (20%) in Taiwanese hereditary nonpolyposis colorectal cancer (HNPCC) is lower than that reported in other countries. This study aimed to examine the microsatellite instability (MSI) status and gene expression pattern of Taiwanese HNPCC in an effort to establish correlation between these data and results of prior genetic screening.
  
  
  METHODS
  The "Bethesda markers" were used for the MSI analysis. Tumor and neighboring tissues were obtained from 10-mm sections of neutral formalin-fixed, paraffin-embedded, hematoxylin and eosin-stained specimens with a PixCell laser-capture microdissector. Four-mm sections were used for the immunohistochemical analysis by avidin-biotin complex method and final coloring with diaminobenzidine. A pathologist performed scoring of the pathological specimens twice, using a double-blinded methodology. Thirteen tissue blocks from 8 HNPCC families (Amsterdam's criteria) were included in this study.
  
  
  RESULTS
  Although the majority of the HNPCC tissues displayed a MSI-high phenotype (10/13, 76.9%), lack of expression of MSH2 and MLH1 was infrequent. Furthermore, only 1 germ-line mutation was detected in the peripheral blood leukocytes of the patients whose tumors had lost protein expression of MSH2 or MLH1.
  
  
  CONCLUSIONS
  Our results indicate that the pathogenesis of Taiwanese HNPCC is different from that in other countries. Rather than immunohistochemical analysis, MSI status, and genetic screening, clinical history remains a reliable method for diagnosis of HNPCC in Taiwanese the population.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and Medical College, No. 7 Chung Shan South Road, Taipei, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Wei
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Jyy-Jih
authors.initials: JJ
authors.lastname: Tsai-Wu
authors.forename: C H Hebert
authors.initials: CH
authors.lastname: Wu
authors.forename: Jin-Chuan
authors.initials: JC
authors.lastname: Sheu
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Jau-Min
authors.initials: JM
authors.lastname: Wong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; 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*; D012680:Sensitivity and Specificity; D013624:Taiwan
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005819:Genetic Markers; 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