Universal Point-of-Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma

BACKGROUND:

Patients with Lynch syndrome (LS) are at risk for upper tract urothelial carcinoma (UTUC). We aim to identify the most reliable means of point-of-care (POC) screening for LS in UTUC patients.

METHODS:

From January 2013 through July 2016, 115 consecutive UTUC patients without a history of LS were universally screened during their follow-up. We evaluated patient/family history (Amsterdam criteria I [AMS1] and II [AMS2]), tumor immunohistochemistry (IHC) for mismatch repair proteins (MMRP), and microsatellite instability (MSI). Patients who were AMS1/2, MSI, or IHC positive were classified as potential Lynch syndrome (pLS) and referred for clinical genetic analysis and counseling (GAC). Patients with known LS were used as positive controls.

RESULTS:

A total of 16/115 (13.9%) patients screened as positive for pLS. Of these, 7.0% met AMS2 criteria, 11.3% had loss of at least one MMRP, and 6.0% had high MSI. All 16 patients were referred for germline testing, 9 completed GAC, and 6 were confirmed to have LS. Of 7 UTUC patients with a known history of LS, all had positive AMS2 criteria and at least a single MMRP loss, 5/6 had high MSI.

CONCLUSIONS:

We identified 13.9% of UTUC cases as pLS and 5.2% with confirmed LS at the POC. These findings have important implications for universal screening of UTUC, representing one of the highest rates of undiagnosed genetic disease in a urologic cancer.

Metcalfe MJ1, Petros FG1, Rao P2, Mork ME3, Xiao L4, Broaddus RR2, Matin SF1

Author information

1 Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

3 Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

4 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

J Urol. 2017 Aug 7. pii: S0022-5347(17)77254-0. doi: 10.1016/j.juro.2017.08.002. [Epub ahead of print]

Read coverage of this abstract presented at the 35th World Congress of Endourology– September 12-16, 2017, Vancouver, Canada.