TY - JOUR
T1 - Immunohistochemistry versus microsatellite instability testing in phenotyping coloreetal tumors
AU - Lindor, Noralane M.
AU - Burgart, Lawrence J.
AU - Leontovich, Olga
AU - Goldberg, Richard M.
AU - Cunningham, Julie M.
AU - Sargent, Daniel J.
AU - Walsh-Vockley, Catherine
AU - Petersen, Gloria M.
AU - Walsh, Michael D.
AU - Leggett, Barbara A.
AU - Young, Joanne P.
AU - Barker, Melissa A.
AU - Jass, Jeremy R.
AU - Hopper, John
AU - Gallinger, Steve
AU - Bapat, Bharati
AU - Redston, Mark
AU - Thibodeau, Stephen N.
PY - 2002/2/15
Y1 - 2002/2/15
N2 - Purpose: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. Patients and Methods: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable. Results: Of 1,144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H. Conclusion: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, costeffective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed.
AB - Purpose: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. Patients and Methods: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable. Results: Of 1,144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H. Conclusion: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, costeffective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed.
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U2 - 10.1200/JCO.20.4.1043
DO - 10.1200/JCO.20.4.1043
M3 - Article
C2 - 11844828
AN - SCOPUS:0037083484
SN - 0732-183X
VL - 20
SP - 1043
EP - 1048
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -