Cost-effective screening using a two-antibody panel for detecting mismatch repair deficiency in sporadic colorectal cancer

BACKGROUND: The microsatellite instability (MSI) test and immunohistochemistry (IHC) are widely used to screen DNA mismatch repair (MMR) deficiency in sporadic colorectal cancer (CRC). For IHC, a two-antibody panel of MLH1 and MSH2 or four-antibody panel of MLH1, MSH2, PMS2, and MSH6 are used. In general, MSI is known as a more accurate screening test than IHC. AIM: To compare two- and four-antibody panels of IHC in terms of accuracy and cost benefit on the basis of MSI testing for detecting MMR deficiency. METHODS: We retrospectively analyzed patients with CRC who underwent curative surgery between 2015 and 2017 at a tertiary referral center. Both IHC with four antibodies and MSI tests were routinely performed. The sensitivity and specificity of a four- and two types of two-antibody panels (PMS2/MSH6 and MLH1/MSH2) were compared on the basis of MSI testing for detecting MMR deficiency. RESULTS: High-frequency MSI was found in 5.5% (n = 193) of the patients (n = 3486). The sensitivities of the four- and two types of two-antibody panels were 97.4%, 92.2%, and 87.6%, respectively. The specificities of the three types of panels did not differ significantly (99.6% for the four-antibody and PMS2/MSH6 panels, 99.7% for the MLH1/MSH2 panel). Based on Cohen's kappa statistic (κ), four- and two-antibody panels were in almost perfect agreement with the MSI test (κ > 0.9). The costs of the MSI test and the four- and two-antibody panels of IHC were approximately $200, $160, and $80, respectively. CONCLUSION: Considering the cost of the four-antibody panel IHC compared to that of the two-antibody panel IHC, a two-antibody panel of PMS2/MSH6 might be the best choice in terms of balancing cost-effectiveness and accuracy.