Department of Pathology, Region Kalmar, Kalmar County Hospital, Kalmar, Sweden.
Department of Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden.
BMC Cancer. 2024 Aug 26;24(1):1051. doi: 10.1186/s12885-024-12812-7.
Programmed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones.
Patients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively.
PD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis.
The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.
肿瘤细胞程序性死亡配体 1（PD-L1）的表达与多种恶性肿瘤的预后不良相关，而结直肠癌（CRC）的部分结果则存在矛盾和不确定。本研究旨在通过比较三种不同的抗体克隆来评估 PD-L1 作为 CRC 的预后生物标志物。
本研究回顾性纳入了 2007 年 1 月 1 日至 2015 年 12 月 31 日在瑞典卡尔马县接受手术治疗的 CRC 患者。使用克隆 73-10、SP263 和 22C3 对 862 例未接受新辅助治疗的原发性肿瘤的组织微阵列进行肿瘤细胞（TC）和免疫细胞（IC）的免疫组织化学表达 PD-L1 检测。单变量和多变量分析中，使用 Cox 回归比例风险模型估计总生存（OS）和无病间隔（DFI）的风险比，分别以 1%和 5%作为 TC 和 IC 阳性表达的截断值。
克隆 73-10、克隆 SP263 和克隆 22C3 检测到 TC 中 PD-L1 表达的病例分别为 89（10%）、76（9%）和 38（4%），而 IC 中 PD-L1 表达的病例分别为 317（37%）、264（31%）和 89（10%）。在单变量分析中，所有三种克隆的 IC 中 PD-L1 表达与 OS 和 DFI 延长相关。在多变量分析中，73-10 和 SP263 与 DFI 延长相关，但仅 73-10 与 OS 延长相关。TC 中 PD-L1 表达与 OS 无相关性，但与 SP263 的 DFI 延长相关，而 73-10 则呈现出趋势。在多变量分析中，SP263 的 DFI 延长相关性仍然存在，而 73-10 的相关性则得到加强。
不同抗体克隆中，TC 和 IC 中 PD-L1 表达的预后价值不同，与 22C3 相比，克隆 73-10 和 SP263 为结直肠癌的预后信息提供了更可靠的依据。
