Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Thorac Cancer. 2022 Feb;13(4):523-532. doi: 10.1111/1759-7714.14285. Epub 2021 Dec 24.
The combined positive score (CPS) of the programmed death ligand-1 (PD-L1) 22C3 assay is a predictive marker of pembrolizumab monotherapy for advanced esophageal cancer (EC) patients. However, little is known about the association of the PD-L1 22C3 CPS with the clinicopathological features and heterogeneity of PD-L1 expression in EC in the Chinese population in a real-world setting.
We examined the association of the PD-L1 22C3 CPS with clinicopathological characteristics in 533 EC specimens. Further, we compared 37 cases' different blocks of the same specimen and 50 paired primary/metastatic lymph node lesions to investigate the heterogeneity of PD-L1 expression.
PD-L1 positive expression was observed in 45.0% of 533 EC patients, including 46.8% with squamous cell carcinoma, 15.4% with adenocarcinoma, 28.6% with basaloid squamous carcinoma, 42.9% with spindle cell carcinoma, and 33.3% with neuroendocrine tumors. PD-L1 positive expression was positively associated with lymph node metastasis (59.2% chance, p = 0.021) and venous/lymphatic invasion (66.3% chance, p = 0.029). PD-L1 expression was highly consistent in different paraffin blocks of the same surgically resected specimen (concordance rate: 86.5%, p = 0.000016) and a moderate consistency (concordance rate: 78.0%, p = 0.000373) for the primary and metastatic lymph node lesion comparison.
This is a novel study which demonstrated a positive correlation between a high PD-L1 22C3 CPS and invasion/metastasis risk in EC surgical specimens. Both paired blocks and paired primary/metastatic lymph node lesions showed significant concordance. PD-L1 heterogeneity was inferred to be mainly related to positive mononuclear inflammatory cells (MICs), which might have substantial implications for clinical practice.
程序性死亡配体-1（PD-L1）22C3 检测的联合阳性评分（CPS）是预测帕博利珠单抗单药治疗晚期食管癌（EC）患者的标志物。然而，在真实世界环境中，关于 PD-L1 22C3 CPS 与中国人 EC 患者的临床病理特征和 PD-L1 表达异质性的关系知之甚少。
我们研究了 533 例 EC 标本中 PD-L1 22C3 CPS 与临床病理特征的关系。此外，我们比较了 37 例同一标本的不同组织块和 50 对原发/转移性淋巴结病变，以研究 PD-L1 表达的异质性。
533 例 EC 患者中观察到 45.0%的 PD-L1 阳性表达，其中鳞癌占 46.8%，腺癌占 15.4%，基底样鳞状细胞癌占 28.6%，梭形细胞癌占 42.9%，神经内分泌肿瘤占 33.3%。PD-L1 阳性表达与淋巴结转移（59.2%的机会，p=0.021）和静脉/淋巴浸润（66.3%的机会，p=0.029）呈正相关。在同一手术切除标本的不同石蜡块中，PD-L1 表达高度一致（一致性率：86.5%，p=0.000016），在原发和转移性淋巴结病变的比较中，一致性中等（一致性率：78.0%，p=0.000373）。
这是一项新的研究，表明 PD-L1 22C3 CPS 高与 EC 手术标本的侵袭/转移风险呈正相关。配对的组织块和配对的原发/转移性淋巴结病变均显示出显著的一致性。PD-L1 异质性推断主要与阳性单核炎性细胞（MICs）有关，这可能对临床实践有重要意义。
