Stephanie A M Wankowicz1, Lillian Werner2, Anna Orsola1, Jesse Novak3, Michaela Bowden4, Toni K Choueiri5, Inés de Torres6, Juan Morote7, Gordon J Freeman8, Sabina Signoretti9, Joaquim Bellmunt10. 1. Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts. 2. Department of Biostatistics, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts. 3. Department of Pathology, Brigham and Women's Cancer Center, Boston, Massachusetts. 4. Department of Medical Oncology, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts. 5. Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 6. Department of Pathology, Vall d'Hebron Hospital, Barcelona, Spain. 7. Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain. 8. Department of Medical Oncology, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 9. Department of Pathology, Brigham and Women's Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. 10. Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address: Joaquim_bellmunt@dfci.harvard.edu.
Abstract
PURPOSE: PD-L1 is expressed on tumor cells and tumor immune cell infiltrates. In metastatic bladder cancer increased tumor immune cell infiltrate PD-L1 positivity correlated with better overall survival. However, to our knowledge in high grade T1 bladder tumors positivity on tumor cells and tumor immune cell infiltrates, and correlation with outcomes or pathological features remain unknown. MATERIALS AND METHODS: Formalin fixed, paraffin embedded tumor samples from 140 patients with clinically annotated, high grade T1 bladder tumors were retrieved. All patients were initially diagnosed with high grade T1 bladder tumors by transurethral resection, subsequently received bacillus Calmette-Guérin and had a median followup of 7.4 years. PD-L1 positivity on initial transurethral resection was evaluated by immunohistochemistry using a mouse monoclonal antiPD-L1 antibody (405.9A11). Tumor cell PD-L1 positivity was defined as staining of 5% of the tumor cell membrane. Tumor immune cell infiltrate PD-L1 positivity was scored based on the extent of infiltrate and the percent of positive cells. The Fisher exact test was used to assess associations of PD-L1 positivity with disease outcomes, carcinoma in situ presence and the difference between high grade T1 bladder tumors and muscle invasive bladder cancer. RESULTS: Among 140 patients with high grade T1 bladder tumors tumor cells and tumor immune cell infiltrate PD-L1 positivity was seen in 6 (4%) and 48 (34.3%), respectively. In a subset of 106 patients with adequate followup PD-L1 positivity did not correlate with disease outcomes on tumor cells (p = 0.3) or on tumor immune cell infiltrates (p = 0.47). PD-L1 positivity also did not correlate with the presence of carcinoma in situ. Tumor cell PD-L1 positivity was significantly less in high grade T1 bladder tumors than in muscle invasive bladder cancer (p <0.001). CONCLUSIONS: PD-L1 is widely expressed on tumor immune cell infiltrates but not on tumor cells in high grade T1 bladder tumors. We did not find a correlation between PD-L1 positivity and outcomes or carcinoma in situ presence. Tumor cell PD-L1 positivity is significantly lower in high grade T1 bladder tumors than in muscle invasive bladder cancer.
PURPOSE:PD-L1 is expressed on tumor cells and tumor immune cell infiltrates. In metastatic bladder cancer increased tumor immune cell infiltrate PD-L1 positivity correlated with better overall survival. However, to our knowledge in high grade T1 bladder tumors positivity on tumor cells and tumor immune cell infiltrates, and correlation with outcomes or pathological features remain unknown. MATERIALS AND METHODS:Formalin fixed, paraffin embedded tumor samples from 140 patients with clinically annotated, high grade T1 bladder tumors were retrieved. All patients were initially diagnosed with high grade T1 bladder tumors by transurethral resection, subsequently received bacillus Calmette-Guérin and had a median followup of 7.4 years. PD-L1 positivity on initial transurethral resection was evaluated by immunohistochemistry using a mouse monoclonal antiPD-L1 antibody (405.9A11). Tumor cell PD-L1 positivity was defined as staining of 5% of the tumor cell membrane. Tumor immune cell infiltrate PD-L1 positivity was scored based on the extent of infiltrate and the percent of positive cells. The Fisher exact test was used to assess associations of PD-L1 positivity with disease outcomes, carcinoma in situ presence and the difference between high grade T1 bladder tumors and muscle invasive bladder cancer. RESULTS: Among 140 patients with high grade T1 bladder tumors tumor cells and tumor immune cell infiltrate PD-L1 positivity was seen in 6 (4%) and 48 (34.3%), respectively. In a subset of 106 patients with adequate followup PD-L1 positivity did not correlate with disease outcomes on tumor cells (p = 0.3) or on tumor immune cell infiltrates (p = 0.47). PD-L1 positivity also did not correlate with the presence of carcinoma in situ. Tumor cell PD-L1 positivity was significantly less in high grade T1 bladder tumors than in muscle invasive bladder cancer (p <0.001). CONCLUSIONS:PD-L1 is widely expressed on tumor immune cell infiltrates but not on tumor cells in high grade T1 bladder tumors. We did not find a correlation between PD-L1 positivity and outcomes or carcinoma in situ presence. Tumor cell PD-L1 positivity is significantly lower in high grade T1 bladder tumors than in muscle invasive bladder cancer.
Authors: Henning Reis; Rene Serrette; Jennifer Posada; Vincent Lu; Ying-Bei Chen; Anuradha Gopalan; Samson W Fine; Satish K Tickoo; Sahussapont J Sirintrapun; Gopa Iyer; Samuel A Funt; Min Yuen Teo; Jonathan E Rosenberg; Dean F Bajorin; Guido Dalbagni; Bernard H Bochner; David B Solit; Victor E Reuter; Hikmat A Al-Ahmadie Journal: Am J Surg Pathol Date: 2019-07 Impact factor: 6.394
Authors: Toni K Choueiri; Sabina Signoretti; Abdallah Flaifel; Wanling Xie; David A Braun; Miriam Ficial; Ziad Bakouny; Amin H Nassar; Rebecca B Jennings; Bernard Escudier; Daniel J George; Robert J Motzer; Michael J Morris; Thomas Powles; Evelyn Wang; Ying Huang; Gordon J Freeman Journal: Clin Cancer Res Date: 2019-08-01 Impact factor: 12.531
Authors: Ramy R Saleh; Jordan L Scott; Nicholas Meti; Danielle Perlon; Rouhi Fazelzad; Alberto Ocana; Eitan Amir Journal: Mol Diagn Ther Date: 2022-02-01 Impact factor: 4.074
Authors: Rui Batista; Nuno Vinagre; Sara Meireles; João Vinagre; Hugo Prazeres; Ricardo Leão; Valdemar Máximo; Paula Soares Journal: Diagnostics (Basel) Date: 2020-01-13