Determination of Mismatch Repair Status in Human Cancer and Its Clinical Significance Does One Size Fit All?Corti, Chiara, MD; Sajjadi, Elham, MD; Fusco, Nicola, MDAdvances in Anatomic Pathology: July 2019 - Volume 26 - Issue 4 - p 270–279 doi: 10.1097/PAP.0000000000000234 Review Articles Buy Abstract Author InformationAuthors Article MetricsMetrics The clinical management of cancers has progressed rapidly into the immunopathology era, with the unprecedented histology-agnostic approval of pembrolizumab in mismatch repair (MMR) deficient tumors. Despite the significant recent achievements in the treatment of these patients, however, the identification of clinically relevant subclasses of cancers based on the MMR status remains a major challenge. Many investigations have assessed the role of different diagnostic tools, including immunohistochemistry, microsatellite instability, and tumor mutational burden in both prognostic and therapeutic settings, with heterogenous results. To date, there are no tumor-specific guidelines or companion diagnostic tests for MMR assessment, and this analysis is often performed with locally developed methods. In this review, we provide a comprehensive overview of the current state-of-knowledge of MMR alterations in syndromic and sporadic tumors and discuss the available armamentarium for MMR pathologic characterization, from morphology to high-throughput molecular tools. Division of Pathology, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, University of Milan, Milan, Italy The authors declare no competing financial interests, including funding received from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s). The authors have no funding or conflicts of interest to disclose. All figures can be viewed online in color at www.anatomicpathology.com. Reprints: Nicola Fusco, MD, Division of Pathology, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan 20122, Italy (e-mail: firstname.lastname@example.org). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.