Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts.
Department of Biostatistics, Dana-Farber Cancer Institute/Brigham and Women's Cancer Center, Boston, Massachusetts.
J Urol. 2017 Oct;198(4):817-823. doi: 10.1016/j.juro.2017.04.102. Epub 2017 May 6.
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.
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.
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).
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.
PD-L1 表达于肿瘤细胞和肿瘤浸润免疫细胞。在转移性膀胱癌中，肿瘤浸润免疫细胞 PD-L1 阳性与总生存改善相关。然而，据我们所知，在高级别 T1 膀胱肿瘤中，肿瘤细胞和肿瘤浸润免疫细胞的 PD-L1 阳性率及其与结局或病理特征的相关性尚不清楚。
从 140 例临床标注的高级别 T1 膀胱肿瘤患者的福尔马林固定、石蜡包埋肿瘤标本中获取组织。所有患者均经经尿道膀胱肿瘤切除术初诊为高级别 T1 膀胱癌，随后接受卡介苗治疗，中位随访时间为 7.4 年。采用小鼠抗 PD-L1 单克隆抗体（405.9A11）进行免疫组织化学检测，评估初始经尿道膀胱肿瘤切除术时的 PD-L1 阳性率。肿瘤细胞 PD-L1 阳性定义为肿瘤细胞膜 5%的染色。根据浸润程度和阳性细胞百分比对肿瘤浸润免疫细胞 PD-L1 阳性率进行评分。采用 Fisher 确切概率法评估 PD-L1 阳性与疾病结局、原位癌存在及高级别 T1 膀胱癌与肌层浸润性膀胱癌之间的差异。
在 140 例高级别 T1 膀胱肿瘤患者中，肿瘤细胞和肿瘤浸润免疫细胞 PD-L1 阳性率分别为 6（4%）和 48（34.3%）。在 106 例有足够随访的患者亚组中，肿瘤细胞 PD-L1 阳性与疾病结局（p = 0.3）或肿瘤浸润免疫细胞 PD-L1 阳性（p = 0.47）均无相关性。PD-L1 阳性与原位癌的存在也无相关性。高级别 T1 膀胱肿瘤的肿瘤细胞 PD-L1 阳性率显著低于肌层浸润性膀胱癌（p<0.001）。
PD-L1 在高级别 T1 膀胱肿瘤的肿瘤浸润免疫细胞中广泛表达，但在肿瘤细胞中不表达。我们未发现 PD-L1 阳性与结局或原位癌存在之间的相关性。高级别 T1 膀胱肿瘤的肿瘤细胞 PD-L1 阳性率显著低于肌层浸润性膀胱癌。
