Increased PD-L1 expression in high-grade bladder cancer with squamous cell differentiation in Bulgarian and French patients' samples.

Urothelial carcinomas (UC) of the bladder are biologically and clinically heterogeneous and the most common malignancy of the urinary tract in developed countries worldwide, where several checkpoint targets as programmed death ligand-1 (PD-L1) and programmed cell death protein (PD-1) have received the most attention in the treatment of bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established enough. To evaluate programmed death ligand-1 (PD-L1) expression in UCs of the bladder in Bulgarian and French patients' samples. Urothelial bladder carcinomas cases from 2016-2020 were retrospectively were analyzed. The cohort included 105 cases: 42 (40%) low grade and 63 (60%) high grade. Immunohistochemical (IHC) staining for PD-L1 expression was performed using an anti-PD-L1 primary antibody clone 22C3pharmDx only to 73/105 cases. Approximately 21/73 cases (28.8%) of urothelial bladder carcinomas demonstrated positive PD-L1 expression, and in 52/73 cases (71.2%) were negative. Positive PD-L1 expression was associated with high grade and high pathologic stage (p < 0.001). We found that PD-L1 was expressed in a significant percentage in UC with squamous differentiation (40%), followed by classic UC (30%). An association between histological grading systems of bladder UC (WHO1973 and WHO 2016) and the TNM-staging system, estimated by Pearson correlation coefficients (r = 0.590 and r = 0.583, respectively, p < 0.001) was observed. We found that PD-L1 expression is increased in patients with muscle-invasive UC, and PD-L1 might be a new biomarker that correlates with the pathological stage of urothelial bladder cancer and might predict recurrence-free survival.

Gulinac M ，Dikov D ，Velikova T ，Belovezhdov V ... -  《-》

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.

Skala SL ，Liu TY ，Udager AM ，Weizer AZ ，Montgomery JS ，Palapattu GS ，Siddiqui J ，Cao X ，Fields K ，Abugharib AE ，Soliman M ，Hafez KS ，Miller D ，Lee CT ，Alva A ，Chinnaiyan AM ，Morgan TM ，Spratt DE ，Jiang H ，Mehra R ... -  《European Urology Focus》

PD-L1 expression in tumor cells and the immunologic milieu of bladder carcinomas: a pathologic review of 165 cases.

Programmed death ligand 1 (PD-L1) is a transmembrane protein that plays a major role in immune suppression. Its interaction with the receptor PD-1 results in downregulation of antitumoral immunity. Humanized monoclonal antibodies that interrupt the PD-L1/PD-1 interaction have shown therapeutic efficacy in patients with advanced urothelial cancer. However, immunohistochemical staining of PD-L1 in bladder tumors and its relationship to tumor histologic type, grade, and overall survival has been incompletely analyzed. Slides from 165 cystectomy specimens were reviewed for tumor type, grade of urothelial carcinoma, pathologic stage, and overall survival. A tissue microarray (TMA) using four 0.6 mm cores from each case was constructed. Immunohistochemistry was performed on the TMA using a variety of new PD-L1 antibodies and platforms now widely available. For each case, the percent of tumor cells positive for PD-L1 and the percent of positive immune cells were scored. The overall number of bladder cancers positive for PD-L1 depended on the antibody/platform combination used and the threshold for considering a tumor "PD-L1-positive." Squamous cell carcinomas (SCCs) of the bladder demonstrated PD-L1 positivity more frequently than urothelial cell carcinomas (UCCs). High-grade UCCs were positive for PD-L1 on tumor cells more frequently than low-grade UCCs. There was no difference in survival between PD-L1-positive and PD-L1-negative bladder cancers in our study. Further studies should consider examining the predictive significance of PD-L1 IHC in bladder cancers.

Davick JJ ，Frierson HF ，Smolkin M ，Gru AA ... -  《-》

The Significance of Squamous Histology on Clinical Outcomes and PD-L1 Expression in Bladder Cancer.

Gordetsky JB ，Montgomery KW ，Giannico GA ，Rais-Bahrami S ，Thapa P ，Boorjian S ，Frank I ，Cheville J ... -  《-》

PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression.

Inman BA ，Sebo TJ ，Frigola X ，Dong H ，Bergstralh EJ ，Frank I ，Fradet Y ，Lacombe L ，Kwon ED ... -  《CANCER》