Departments of Pathology.
Department of Pathology, Parkland Hospital, Dallas, TX.
Am J Surg Pathol. 2021 Jun 1;45(6):742-752. doi: 10.1097/PAS.0000000000001633.
Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8+ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P=0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PD-L1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P=0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8+ tumor-infiltrating lymphocyte density (CPS: P=0.028; TPS: P=0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR]=4.253 vs. 0.235, P=0.025; TPS: HR=4.98 vs. 0.2; P=0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR=6.15 vs. 0.16, P=0.045; TPS: HR=3.78 vs. 0.26, P=0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PD-L1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.
程序性死亡配体 1（PD-L1）的表达已被用作预测免疫检查点抑制剂反应的标志物，并被报道具有预后价值。其在宫颈内膜腺癌（ECA）中的流行程度和意义仍有待研究。我们评估了 89 例 ECA 全组织切片中的 PD-L1 表达和 CD8+肿瘤浸润淋巴细胞密度。通过联合阳性评分（CPS，cutoff 1），68%的 ECA 观察到 PD-L1 表达，通过肿瘤比例评分（TPS，cutoff 1），29%的 ECA 观察到 PD-L1 表达。使用 CPS，模式 A、B 和 C 肿瘤的 PD-L1 表达分别为 11%、78%和 72%，具有破坏性侵袭（B 和 C）的肿瘤表达明显更高（P=0.001[A 与 B]，0.0006[A 与 C]，0.0002[A 与 B+C]）。使用 TPS，不同侵袭模式的肿瘤之间 PD-L1 表达无显著差异（模式 A、B 和 C 的肿瘤分别为 0%、22%和 32%；P=0.27[A 与 B]，0.053[A 与 C]，0.11[A 与 B+C]）。与 PD-L1 阴性 ECA 相比，PD-L1 阳性 ECA 显示出更高的 CD8+肿瘤浸润淋巴细胞密度（CPS：P=0.028；TPS：P=0.013）和更差的无进展生存率（CPS：危险比[HR]=4.253 与 0.235，P=0.025；TPS：HR=4.98 与 0.2；P=0.004）。当单独评估侵袭模式时，模式 C 肿瘤中 PD-L1 阳性肿瘤的无进展生存率也较差（CPS：HR=6.15 与 0.16，P=0.045；TPS：HR=3.78 与 0.26，P=0.027）。总之，我们的数据显示，具有破坏性侵袭的 ECA 中 PD-L1 表达频繁，支持 PD-1/PD-L1 通路作为这些肿瘤的治疗靶点。我们的数据还支持 PD-L1 作为与潜在不良预后相关的阴性预后标志物。
