Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 26, 2021; 9(24): 6999-7008
Published online Aug 26, 2021. doi: 10.12998/wjcc.v9.i24.6999
Cost-effective screening using a two-antibody panel for detecting mismatch repair deficiency in sporadic colorectal cancer
Jong Beom Kim, Young Il Kim, Yong Sik Yoon, Jihun Kim, Seo Young Park, Jong Lyul Lee, Chan Wook Kim, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim
Jong Beom Kim, Young Il Kim, Yong Sik Yoon, Jong Lyul Lee, Chan Wook Kim, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim, Division of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Jihun Kim, Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Seo Young Park, Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
Author contributions: Kim JB and Kim YI contributed equally to this article. Kim JB contributed to data acquisition, analysis, interpretation, and wrote the paper; Yoon YS contributed to research design, and supervised the report; Kim J contributed to research design, and contributed to the analysis; Kim YI revised the manuscript; Yoon YS, Kim J should be considered as joint corresponding authors; Park SY proposed an appropriate statistical analysis method; Kim YI, Lee JL, Kim CW, Park IJ, Lim SB, Yu CS, Kim JC provided clinical advice; all authors read and approved the manuscript.
Supported by the Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea, No. 2020IP0039.
Institutional review board statement: The study’s protocol was reviewed and approved by the institutional review board of our institution (IRB No. 2019-7777).
Informed consent statement: Data was anonymous and informed consent was waived by the IRB.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong Sik Yoon, MD, PhD, Professor, Division of Colon and Rectal Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. yoonys@amc.seoul.kr
Received: December 29, 2020
Peer-review started: December 29, 2020
First decision: May 2, 2021
Revised: May 24, 2021
Accepted: July 23, 2021
Article in press: July 23, 2021
Published online: August 26, 2021
ARTICLE HIGHLIGHTS
Research 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.

Research motivation

Several studies have compared four- and two-antibody panels in terms of accuracy and cost-effectiveness. However, large-scale studies examining all four types of IHC and comparing two- vs four-antibody panel of IHC are rare.

Research objectives

This study aimed 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.

Research 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.

Research 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.

Research conclusions

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.

Research perspectives

Based on this study, medical policy could be altered to minimize expense for detecting MMR deficiency. Further studies including multicenter from different nations is needed for a more accurate comparison and additional assessment of oncologic outcomes.