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

Abstract

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 (k), four- and two-antibody panels were in almost perfect agreement with the MSI test (k > 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.