Department of Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, PA.
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia.
Am J Clin Pathol. 2019 May 3;151(6):561-573. doi: 10.1093/ajcp/aqz002.
Limited literature is available on the tumor microenvironment (TM) of upper tract urothelial carcinoma (UTUC). This study comprehensively reviews programmed death 1 receptor (PD-1)-positive and CD8+ tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on tumor epithelium (TE).
Seventy-two nephroureterectomy specimens were analyzed for PD-L1, PD-1, and CD8. One percent or more tumor and lymphohistiocyte PD-L1 expression was considered positive. TIL density by H&E was scored semiquantitatively from 0 to 3, and CD8+ and PD-1+ TILs were quantified in hotspots.
Of the cases, 37.5% demonstrated PD-L1+ on TE. PD-L1+ TE showed an association with pathologic stage (P = .01), squamous differentiation (SqD) (P < .001), TILs by H&E (P = .02), PD-1+ peritumoral TILs (P = .01), and PD-L1+ peritumoral lymphohistiocytes (P = .002). Finally, there was a significant difference in PD-1+ peritumoral TILs in cases with SqD vs no SqD (P = .03).
Aggressive UTUC is associated with a distinct TM. Furthermore, TM of UTUC-SqD was distinctly different from those with no SqD, warranting study in a larger cohort.
有关上尿路上皮癌（UTUC）肿瘤微环境（TM）的文献有限。本研究全面回顾了程序性死亡受体 1（PD-1）阳性和 CD8+肿瘤浸润淋巴细胞（TIL）以及肿瘤上皮（TE）中程序性死亡配体 1（PD-L1）的表达。
分析了 72 例肾输尿管切除术标本的 PD-L1、PD-1 和 CD8。肿瘤和淋巴组织细胞 PD-L1 表达 1%或以上被认为是阳性。用 H&E 对 TIL 密度进行半定量评分，从 0 到 3 分，并在热点处对 CD8+和 PD-1+TIL 进行定量。
在这些病例中，37.5%的 TE 显示 PD-L1+。PD-L1+TE 与病理分期（P=0.01）、鳞状分化（SqD）（P<0.001）、H&E 所示 TIL（P=0.02）、肿瘤周围 PD-1+TIL（P=0.01）和肿瘤周围 PD-L1+淋巴组织细胞（P=0.002）有关。最后，在有 SqD 和无 SqD 的病例中，肿瘤周围 PD-1+TIL 有显著差异（P=0.03）。
侵袭性 UTUC 与独特的 TM 相关。此外，UTUC-SqD 的 TM 与无 SqD 的 TM 明显不同，值得在更大的队列中进行研究。
