Clinical and molecular analysis of hereditary non-polyposis colorectal cancer in Chinese colorectal cancer patients.
OBJECTIVE
To analyze the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in Chinese colorectal cancer (CRC) patients, and to discuss the value of microsatellite instability (MSI) and/or immunohistochemistry (IHC) for MSH2/MLH1 protein analysis as pre-screening tests in China.


METHODS
The Amsterdam criteria I and II (clinical diagnosis) and/or germline hMLH1/hMSH2 mutations (genetic diagnosis) were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband.


RESULTS
From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients (5.7%) from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively.


CONCLUSIONS
The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable pre-screening tests for hMLH1/hMSH2 germline mutations in families suspected of having HNPCC.
Wang
Jun
J
Hereditary Colorectal Tumors Registry, Tianjin Binjiang Hospital, Tianjin 300022, China. Binjiang chinahcc@vip.sina.com
Luo
Mao-Hong
MH
Zhang
Zuo-Xing
ZX
Zhang
Pei-Da
PD
Jiang
Xi-Li
XL
Ma
Dong-Wang
DW
Suo
Rong-Zeng
RZ
Zhao
Li-Zhong
LZ
Qi
Qing-Hui
QH
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation / Q000235:genetics; D017408:Guidelines as Topic; D006801:Humans; D015994:Incidence; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein