Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors.
OBJECTIVE
To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer.


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.


CONCLUSIONS
IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, cost-effective, 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.
Lindor
Noralane M
NM
Department of Medical Genetics, Mayo Foundation, Rochester, MN 55905, USA. nlindor@mayo.edu
Burgart
Lawrence J
LJ
Leontovich
Olga
O
Goldberg
Richard M
RM
Cunningham
Julie M
JM
Sargent
Daniel J
DJ
Walsh-Vockley
Catherine
C
Petersen
Gloria M
GM
Walsh
Michael D
MD
Leggett
Barbara A
BA
Young
Joanne P
JP
Barker
Melissa A
MA
Jass
Jeremy R
JR
Hopper
John
J
Gallinger
Steve
S
Bapat
Bharati
B
Redston
Mark
M
Thibodeau
Stephen N
SN
D000368:Aged; D020137:Base Pair Mismatch / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003362:Cost-Benefit Analysis; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm