Preprint Article Version 1 This version is not peer-reviewed

Evaluation of DNA Mismatch Repair Proteins by Immunohistochemistry Using Two Antibodies

Version 1 : Received: 9 October 2024 / Approved: 9 October 2024 / Online: 9 October 2024 (11:04:53 CEST)

How to cite: Lino-Silvca, L. S.; Salazar-Castillo, M.; Balderas-López, S. F.; Martínez-Villavicencio, S. B.; Rivera-Moncada, L. F.; Ortega-Martínez, H. I.; Zepeda-Najar, C. Evaluation of DNA Mismatch Repair Proteins by Immunohistochemistry Using Two Antibodies. Preprints 2024, 2024100684. https://doi.org/10.20944/preprints202410.0684.v1 Lino-Silvca, L. S.; Salazar-Castillo, M.; Balderas-López, S. F.; Martínez-Villavicencio, S. B.; Rivera-Moncada, L. F.; Ortega-Martínez, H. I.; Zepeda-Najar, C. Evaluation of DNA Mismatch Repair Proteins by Immunohistochemistry Using Two Antibodies. Preprints 2024, 2024100684. https://doi.org/10.20944/preprints202410.0684.v1

Abstract

Background: Determining the status of DNA mismatch repair (MMR) proteins is crucial for guiding treatment decisions and predicting prognosis in patients with colorectal cancer. This study evaluates a streamlined panel utilizing two antibodies for MMR protein assessment, aiming to enhance cost-effectiveness, reduce workload, and expedite result delivery. Methods: We re-classified patients with adenocarcinoma requiring MMR determination by evaluating only PMS2 and MSH6 proteins. The diagnostic performance of the proposed two-antibody panel was compared to the traditional four-antibody panel against a polymerase chain reaction (PCR) assay used as the reference standard. Results: A total of 404 cases were analyzed, with the predominant histological type being adenocarcinoma not otherwise specified. The most common histological grade was 2, and 60.9% of cases were in clinical stage II. Comparative analysis showed no statistically significant differences between the two-antibody and four-antibody panels. Sensitivity was 95.35% for the four-antibody panel versus 90.7% for the two-antibody panel; specificity was 98.74% versus 98.11%, respectively. Additionally, the positive predictive value was 95.35% for the four-antibody panel compared to 92.86% for the two-antibody panel, and negative predictive values were 98.74% versus 97.50%. The area under the curve was 0.970 for the four-antibody panel and 0.944 for the two-antibody panel (p=0.419). Conclusion: The analysis shows that determining MMR status using only two antibodies is as effective as employing a traditional four-antibody panel, providing a viable, cost-effective alternative for clinical practice.

Keywords

microsatellite instability; mismatch repair; colon cancer; adenocarcinoma; diagnostic performance

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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