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Olumide Gbolahan, Neda Hashemi-Sadraei and Bert O’Neil

absence of microsatellite instability (MSI). On the basis of high TMB, the patient was started on anti–PD-1 antibody therapy (nivolumab) in March 2017. Interval imaging 2 months after initiation of therapy showed a stable 1.5-cm left hepatic lobe nodule, a

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Axel Grothey and Alan P. Venook

mutually exclusive—a fact that can guide the ordering of the tests. Clinicians should test for the status of microsatellite instability (MSI; also known as mismatch repair [MMR] deficiency). Patients who are MSI-high or MMR-deficient (“2 ways of looking

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Jeremy Matloff, Aimee Lucas, Alexandros D. Polydorides and Steven H. Itzkowitz

developed to extend the recognition of LS by analyzing tumors for the characteristic microsatellite instability (MSI) phenotype. Bethesda criteria suggest that tumors should be tested for MSI if any of the following criteria are met: 1) CRC at an age younger

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David Y. Oh, Alan P. Venook and Lawrence Fong

. 37. Gatalica Z Snyder CL Yeatts K . Programmed death 1 (PD-1) lymphocytes and ligand (PD-L1) in colorectal cancer and their relationship to microsatellite instability status [abstract] . J Clin Oncol 2014 ; 32 ( Suppl ): Abstract 3625

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Jun Gong, Chongkai Wang, Peter P. Lee, Peiguo Chu and Marwan Fakih

nonregional retroperitoneal lymph nodes. His recurrent disease was not deemed curatively resectable. Microsatellite instability (MSI) testing via polymerase chain reaction analysis showed that the recurrent tumor was MSS. Furthermore, next

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Katherine M. Bever and Dung T. Le

Lynch HT . Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma . Cancer 2001 ; 91 : 2417 – 2422 . 10. Rosenbaum MW Bledsoe JR Morales-Oyarvide V . PD-L1 expression in colorectal cancer is

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Emil Lou, Donna D'Souza and Andrew C. Nelson

assessment for microsatellite instability. (A) Hematoxylin-eosin stain of primary colon tumor (original magnification x20). (B–E) Immunohistochemistry (original magnification x20) shows protein expression of (B) MLH1, (C) PMS2, (D) MSH2, and (E) MSH6

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Ronan J. Kelly

Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been incremental at best. Esophageal cancer requires a concerted multidisciplinary approach, perhaps more so than any other tumor type given the integral role played by the esophagus in maintaining calorific intake and the propensity for early spread through the lymphatics. This review describes the latest in surgical techniques to minimize postoperative complications and examines previous and ongoing systemic therapy approaches. Strategies that harness a patient’s own immune system hold great promise, and shifting checkpoint inhibitors from the metastatic setting to the neoadjuvant/adjuvant setting is currently being evaluated in phase II and III clinical trials. In addition, a much better understanding of the interplay between tumors and their immune microenvironment is clearly needed to better judge how best to engage each patient’s immune system, and there will be likely demonstrable differences between early-stage tumors and metastatic disease. This review highlights emerging data, which demonstrate that, in addition to The Cancer Genome Atlas classification of esophageal squamous cell carcinoma having a distinct molecular makeup compared with esophageal adenocarcinoma, there are also differing responses to PD-1 inhibitors. Histology and the underlying immune milieu may have important ramifications for the management of localized disease in the future, above and beyond PD-L1 expression, microsatellite instability status, and tumor mutational burden.

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Brian Vicuna and Al B. Benson III

Soiland H . Microsatellite instability in colorectal cancer . Br J Surg 2006 ; 93 : 395 – 406 . 17. Boland CR Thibodeau SN Hamilton SR . A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial

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Patrick M. Lynch

– 1762 . 66. Boland CR Thibodeau SN Hamilton SR . A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of