Abstract: PD57-05
Sources of Funding: _x000D_ Supported by the Monteleone Family Foundation for Research in Bladder and Kidney Cancer and the Eleanor and Scott Petty Fund for Upper Tract Urothelial Cancer Research

Introduction

_x000D_ Lynch Syndrome (LS) is an autosomal dominant inherited syndrome that places patients at risk for upper tract urothelial carcinoma (UTUC). Our goal was to identify the most reliable means of screening for LS in patients with UTUC at the point of care (POC).

Methods

_x000D_ Patient information was retrospectively collected in an IRB-approved protocol on patients treated for UTUC. Screening was universally performed on all patients presenting during the study period. We evaluated patient and family history (Amsterdam I and II criteria; AMS1 and AMS2, respectively), tumor immunohistochemistry (IHC) for 4 mismatch repair proteins (MMRP), tumor and normal tissue polymerase-chain reaction for microsatellite instability (MSI), and clinical genetic analysis and counseling (GAC), in those with undiagnosed LS. Patients who were AMS 2 positive, MSI positive of IHC positive were considered as presumed lynch syndrome (pLS).

Results

_x000D_ From 1/2013-7/2016, 101 UTUC patients without a history of LS were universally screened during clinical follow-up. A total of 15/101 (15%) patients were pLS. 7/101 (7%) patients met AMS2 criteria. 4 patients meeting AMS2 criteria had intact expression of MMRP and no MSI instability. 11 (11%) patients had either loss of one or more MMRP. There were two cases of MSI high instability, both in patients with MMRP loss. There were no cases of MSI-high instability and negative IHC. Insufficient tissue was found in 1/101 (1%) of IHC and 8/88 (9%) of MSI tests (p=0.0164). All patients with any positive screen were referred for GAC, 5 followed-up and all 5 patients had a confirmed germline mutation. The remaining did not follow through with GAC because of financial/insurance barriers. _x000D_

Conclusions

_x000D_ We identified 15% of universally screened UTUC as pLS at the POC using IHC and AMS2 criteria. IHC and AMS2 criteria appear to provide the most reliable screening, outperforming AMS1 and MSI. MSI is limited by requirement for normal tissue and a greater amount of tumor tissue, and can miss cases of MMRP loss, especially MSH6. Most patients did not have a personal history of a classic LS-related cancer. Our findings of a 15% rate of LS-related UTUC has significant implications for universal POC testing of UTUC patients. _x000D_ _x000D_

Funding

_x000D_ Supported by the Monteleone Family Foundation for Research in Bladder and Kidney Cancer and the Eleanor and Scott Petty Fund for Upper Tract Urothelial Cancer Research