Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours.
OBJECTIVE
The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing.


METHODS
Tumour samples included in this study were derived from referred patients for screening for hereditary non-polyposis colorectal cancer (HNPCC) and patients who had resections for colorectal cancer that were examined at our institution. MSI was assessed at nine loci (BAT25, BAT26, BAT40, D2S123, D10S197, D17S579, D18S34, D5S346 and D17S250) in all cases. Immunohistochemistry for MLH1 and MSH2 was performed in all cases. Staining for MSH6 and PMS2 was performed in selected cases only.


RESULTS
There were 742 tumours including 661 colorectal lesions and 81 extracolonic tumours of the HNPCC spectrum. Among the 555 MSI-negative tumours, 554 showed an intact protein expression. Amongst the 187 MSI-positive tumours, 126 showed abnormal expression of MLH1 gene protein, 41 showed abnormal expression of MSH2 gene, three showed abnormal expression of MSH6 only, one showed abnormal expression of PMS2 gene protein only and one case showed abnormal expression of all four proteins.


CONCLUSIONS
Immunohistochemistry offers an alternative method for assessment of MSI status which is fast and relatively inexpensive compared with MSI testing. We achieved a sensitivity rate of 92% and specificity of 99.8% for immunohistochemistry testing assessed against the MSI testing. It has to be accepted that a small fraction of MSI-positive cases will be missed by testing with immunohistochemistry alone.
Ruszkiewicz
Andrew
A
Institute of Medical and Veterinary Science, Tissue Pathology, Royal Adelaide Hospital, Adelaide, South Australia. andrew.ruszkiewicz@imvs.sa.gov.au
Bennett
Graeme
G
Moore
James
J
Manavis
Jim
J
Rudzki
Barney
B
Shen
Linda
L
Suthers
Graeme
G
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D012680:Sensitivity and Specificity
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; 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