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Abstract：
OBJECTIVE: Endometrial carcinoma (EC) is the most common cancer of the female genital tract. According to the recently evolved strategies of cancer immunotherapy, immune checkpoints inhibitors are one of the most crucial strategies. Programmed Death Ligand 1 (PD-L1) is an important immune checkpoint regulator. PD-L1 antibodies have shown efficacy in clinical trials of some malignancies. Some of these antibodies have been approved for clinical usage by the Food and Drug Administration (FDA).
METHODS: This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive.
RESULTS: PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively). However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001).
CONCLUSIONS: Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.
METHODS: This retrospective study included a total of 100 ECs, collected from archived, formalin-fixed, paraffin-embedded tissue blocks of hysterectomy specimens of Egyptian females. The samples were immunohistochemically analyzed for PD-L1 expression (in both tumor cells; TCs and tumor infiltrating leucocytes; TILs) by a semiquantitative score (0 to 4), with cutoff points of (0: <1% of the cells, 1: 1% to 4%, 2: 5% to 9%, 3: 10% to 49%, and 4: ≥ 50%). Membranous staining only was considered positive.
RESULTS: PD-L1 was highly expressed in ECs (67% TCs+ and 61% TILs+), with statistically significant relationships with age, lympho-vascular space invasion (LVSI) and TILs score (P = 0.006, 0.016 and <0.005 respectively). However, no statistically significant relationships were detected between PD-L1 expression and the following parameters: histological type, histological grade, pathological stage (pT) or FIGO stage, myometrial, cervical, adnexal/serosal, parametrial involvements and nodal metastasis, as well as ESMO risk stratification system. Moreover, statistically significant relationships were achieved when correlating TILs score with tumor grade and LVSI (P = 0.034 and 0.012 respectively). Also, comparing endometrial hyperplasia (EH) PD-L1 and TCs PDL1 median scores achieved statistically significant relationship (P = 0.001).
CONCLUSIONS: Our results concluded that PD-L1 expression was greater in both TCs and TILs in a subgroup of patients that have advanced age, LVSI and are TILs-rich, identifying them as potential candidates for anti-PD-1/PD-L1 immunotherapy.
摘要：
目的：子宫内膜癌是女性生殖道最常见的恶性肿瘤。根据最近发展起来的癌症免疫治疗策略,免疫检查点抑制剂是最关键的策略之一。程序性死亡配体1(PD-L1)是一种重要的免疫检查点调节因子。PD-L1抗体已在一些恶性肿瘤的临床试验中显示出疗效。这些抗体中的一些已被食品和药物管理局(FDA)批准用于临床使用。
方法：这项回顾性研究共包括100个ECs，从存档中收集，福尔马林固定，埃及女性子宫切除术标本的石蜡包埋组织块。通过半定量评分（0至4）对样品的PD-L1表达进行免疫组织化学分析（在两个肿瘤细胞中；TC和肿瘤浸润白细胞；TIL），截止点为(0:<1%的细胞，1:1%到4%,2：5%到9%，3：10％至49％，和4：≥50%）。仅膜染色被认为是阳性的。
结果：PD-L1在EC中高表达（67%TC+和61%TILs+），与年龄有统计学意义的关系，淋巴管间隙侵犯（LVSI）和TILs评分（分别为P=0.006、0.016和<0.005）。然而,在PD-L1表达与以下参数之间未检测到统计学上的显着关系：组织学类型，组织学分级,病理阶段(pT)或FIGO阶段，子宫肌层,子宫颈,附件/浆膜，宫旁受累和淋巴结转移，以及ESMO风险分层系统。此外，当将TILs评分与肿瘤分级和LVSI相关联时,达到统计学显著的相关性(分别为P=0.034和0.012).此外，比较子宫内膜增生(EH)PD-L1和TCsPDL1中位评分,取得了统计学显著的相关性(P=0.001).
结论：我们的结果得出结论，在高龄患者的亚组中，TC和TILs中的PD-L1表达更高，LVSI和TIL丰富，确定它们是抗PD-1/PD-L1免疫治疗的潜在候选者。
方法：这项回顾性研究共包括100个ECs，从存档中收集，福尔马林固定，埃及女性子宫切除术标本的石蜡包埋组织块。通过半定量评分（0至4）对样品的PD-L1表达进行免疫组织化学分析（在两个肿瘤细胞中；TC和肿瘤浸润白细胞；TIL），截止点为(0:<1%的细胞，1:1%到4%,2：5%到9%，3：10％至49％，和4：≥50%）。仅膜染色被认为是阳性的。
结果：PD-L1在EC中高表达（67%TC+和61%TILs+），与年龄有统计学意义的关系，淋巴管间隙侵犯（LVSI）和TILs评分（分别为P=0.006、0.016和<0.005）。然而,在PD-L1表达与以下参数之间未检测到统计学上的显着关系：组织学类型，组织学分级,病理阶段(pT)或FIGO阶段，子宫肌层,子宫颈,附件/浆膜，宫旁受累和淋巴结转移，以及ESMO风险分层系统。此外，当将TILs评分与肿瘤分级和LVSI相关联时,达到统计学显著的相关性(分别为P=0.034和0.012).此外，比较子宫内膜增生(EH)PD-L1和TCsPDL1中位评分,取得了统计学显著的相关性(P=0.001).
结论：我们的结果得出结论，在高龄患者的亚组中，TC和TILs中的PD-L1表达更高，LVSI和TIL丰富，确定它们是抗PD-1/PD-L1免疫治疗的潜在候选者。
