Microsatellite instability and hMLH1 and hMSH2 gene expression in Taiwanese hereditary nonpolyposis colorectal cancer.
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.
Wei
Shu-Chen
SC
Department of Internal Medicine, National Taiwan University Hospital and Medical College, No. 7 Chung Shan South Road, Taipei, Taiwan.
Shun
Chia-Tung
CT
Tsai-Wu
Jyy-Jih
JJ
Wu
C H Hebert
CH
Sheu
Jin-Chuan
JC
Wang
Cheng-Yi
CY
Wong
Jau-Min
JM
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
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