European urology focus · 2016
Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.
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Skala Stephanie L, Liu Tzu-Ying, Udager Aaron M, Weizer Alon Z, Montgomery Jeffrey S, Palapattu Ganesh S, Siddiqui Javed, Cao Xuhong, Fields Kristina, Abugharib Ahmed E, Soliman Moaaz, Hafez Khaled S, Miller David, Lee Cheryl T, Alva Ajjai, Chinnaiyan Arul M, Morgan Todd M, Spratt Daniel E, Jiang Hui, Mehra Rohit
Аннотация
BACKGROUND: 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.
OBJECTIVE: To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC.
DESIGN, SETTING, AND PARTICIPANTS: 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.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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.
RESULTS AND LIMITATIONS: 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.
CONCLUSIONS: 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.
PATIENT SUMMARY: 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.
OBJECTIVE: To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC.
DESIGN, SETTING, AND PARTICIPANTS: 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.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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.
RESULTS AND LIMITATIONS: 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.
CONCLUSIONS: 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.
PATIENT SUMMARY: 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.