Lynch Syndrome in Japanese Patients with Upper Urinary Tract Carcinoma - Expert Commentary

Lynch syndrome (LS), caused by a mutation in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6PMS2). LS increases the individual’s risk of getting upper urinary tract urothelial carcinoma (UTUC). A recent article published by Ito et al. in the Japanese Journal of Clinical Oncology evaluated the prevalence of LS among UTUC patients. The authors examined clinical and pathological factors associated with the disease, and two LS screening methods microsatellite instability (MSI) and MMR protein immunohistochemistry. The study included 166 tumor samples from 164 UTUC patients.

The researchers found that MSI and IHC results were concordant. They found that four patients had high microsatellite instability and loss of at least one MMR protein by IHC. Three of the four patients were genetically proven to have Lynch syndrome. The fourth patient had features that were highly suggestive for Lynch syndrome based on personal cancer history but did not undergo genetic testing. The prevalence of LS was 1.8% (3/16). The study found an association between microsatellite instability high-level/mismatch repair loss and age < 70 years (P = 0.04), previous history or synchronous diagnosis of colorectal cancer (P < 0.01) and fulfillment of any of the revised Bethesda criteria guidelines (P < 0.01) and ureteric tumor location (P = 0.052) in univariate analysis.

While the majority of UTUCs are sporadic, this study highlights the known association between UTUC and LS. Developing screening and early-prevention strategies for LS patients who are at risk of developing UTUC and their families is an area of active investigation.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


1. Ito, Tetsuya, Koji Kono, Hidetaka Eguchi, Yasushi Okazaki, Gou Yamamoto, Tetsuhiko Tachikawa, Kiwamu Akagi et al. "Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population." Japanese journal of clinical oncology (2019).

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