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