Universal Lynch Syndrome Screening Should be Performed in All Upper Tract Urothelial Carcinomas

The American Journal of Surgical Pathology
Jennifer Y JuHelen P Cathro

Abstract

Lynch syndrome (LS) is defined by germline mutations in DNA mismatch repair (MMR) genes, and affected patients are at high risk for multiple cancers. Reflexive testing for MMR protein loss by immunohistochemistry (IHC) is currently only recommended for colorectal and endometrial cancers, although upper tract urothelial carcinoma (UTUC) is the third-most common malignancy in patients with LS. To study the suitability of universal MMR IHC screening for UTUC, we investigated MMR expression and microsatellite status in UTUC in comparison to bladder UC (BUC), and evaluated the clinicopathologic features of UTUC. We found that 9% of UTUC showed MMR IHC loss (8 MSH6 alone; 1 MSH2 and MSH6; 1 MLH1 and PMS2; n=117) compared with 1% of BUC (1 MSH6 alone; n=160) (P=0.001). Of these, 4/10 (40%) of UTUC (3% overall; 3 MSH6 alone; 1 MLH1 and PMS2) and none (0%) of BUC had high microsatellite instability on molecular testing (P=0.03). The only predictive clinicopathologic feature for MMR loss was a personal history of colorectal cancer (P=0.0003). However, UTUC presents at a similar age to colon carcinoma in LS and thus UTUC may be the sentinel event in some patients. Combining our results with those of other studies suggests that 1% to 3% of...Continue Reading

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Citations

Nov 8, 2018·Endocrine-related Cancer·Xiang ZhangYupei Zhao
Oct 31, 2019·Japanese Journal of Clinical Oncology·Tetsuya ItoHideyuki Ishida
Aug 14, 2020·American Journal of Clinical Pathology·Matthew George GayhartSteven Christopher Smith
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Jul 13, 2021·The American Surgeon·Aaron J ArroyaveJames M McLoughlin
Jan 7, 2021·Archives of Pathology & Laboratory Medicine·Nicholas BaniakMichelle S Hirsch

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