Mismatch Repair Gene Alterations and Microsatellite Instability in Upper Tract Urothelial Carcinoma - Expert Commentary

Lynch Syndrome (LS) is a common hereditary cancer syndrome that is characterized by mutations in the mismatch repair (MMR) genes. The three most common malignancies in LS patients are colorectal, endometrial and upper tract urothelial carcinoma (UTUC). Unlike colorectal and endometrial carcinoma, universal MMR immunohistochemistry (IHC) and microsatellite instability (MSI) testing are not routinely performed in all the UTUC cases.

A new research study published by Ju et al. in The American Journal of Surgical Pathology examined the alterations in the MMR genes and MSI status in UTUC and compared them to bladder urothelial carcinoma (BUC). The investigators obtained tissue samples and patient information from 117 UTUC cases and 160 BUC samples for comparison. The investigators performed immunohistochemical analysis of MMR proteins, cases with with any MMR loss on IHC were tested for MSI status.

The investigators found that 10 cases of UTUC (9%) have MMR alterations compared to only 1% of BUC. 3/4 UTUC cases with MMR loss and high MSI had a history of colorectal carcinoma associated with Lynch syndrome. The only predictive clinical feature for MMR loss was a personal history of colorectal cancer (p=0.0003).

These results are consistent with other studies suggesting that 1-3% of all UTUC cases may represent LS-associated carcinoma. LS accounts for 2% to 6% of both colorectal and endometrial cancers. The authors recommend universal testing for LS screening to be performed in all upper tract urothelial carcinoma patients.

Written By: Bishoy M. Faltas, MD, assistant professor of medicine at Weill Cornell Medicine at New York Presbyterian hospital. 

Read the Abstract

Ju JY, Mills AM, Mahadevan MS, Fan J, Culp SH, Thomas MH, Cathro HP. Am J Surg Pathol. 2018 Aug 24. doi: 10.1097/PAS.0000000000001141.
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