Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes.

To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC.

UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1.

PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model.

Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy.

Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients.

Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are limited, programmed death-ligand 1 positivity in approximately one-third of invasive tumors provides a rational basis for further investigation of programmed death-ligand 1-based immunotherapeutics in these patients.

European urology focus. 2016 Dec 13 [Epub ahead of print]

Stephanie L Skala, Tzu-Ying Liu, Aaron M Udager, Alon Z Weizer, Jeffrey S Montgomery, Ganesh S Palapattu, Javed Siddiqui, Xuhong Cao, Kristina Fields, Ahmed E Abugharib, Moaaz Soliman, Khaled S Hafez, David Miller, Cheryl T Lee, Ajjai Alva, Arul M Chinnaiyan, Todd M Morgan, Daniel E Spratt, Hui Jiang, Rohit Mehra

Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA., Michigan Center for Translational Pathology, Ann Arbor, MI, USA., Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA., Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA., Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA. Electronic address: .

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