Foundation Medicine Inc, Cambridge, Massachusetts, USA
Foundation Medicine Inc, Cambridge, Massachusetts, USA.
J Immunother Cancer. 2021 May;9(5). doi: 10.1136/jitc-2021-002680.
Several studies have shown clinical outcomes data that support the use of ) copy-number (CN) gains and/or losses as a biomarker for immune checkpoint inhibitor (ICPI). Here, we present the landscape of CN changes across a large cohort of solid tumor cases and correlate these with PD-L1 protein expression by immunohistochemistry.
We analyzed all cases that underwent comprehensive genomic profiling (CGP) testing at Foundation Medicine between August 2014 and June 2020. CN changes were correlated with PD-L1 expression in tumor types where there were Food and Drug Administration approved companion diagnostic (CDx) claims and the CDx assay was used to assess PD-L1 expression.
In all, 244 584 samples representing 290 solid tumor types were included in the study. Overall, 17.6% (42 983/244 584) had CN gains (>specimen ploidy), 44.6% (108 970/244 584) were CN neutral, and 37.9% (92 631/244 584) had CN loss. Using different CN cut offs to define positivity resulted in different prevalence estimates: ploidy +1, 17.4% (42 636/244 584); ploidy +2, 6.2% (15 183/244 584); ploidy +3, 2.2% (5375/244 584); ploidy +4, 1.1% (2712/244 584); and ploidy +8, 0.2% (434/244 584). The prevalence of CN changes and CN positivity varied based on tumor type. CN gains were significantly associated with PD-L1 positivity in NSCLC, urothelial carcinoma, breast carcinoma, cervical carcinoma, esophagus squamous cell carcinoma (SCC) and head and neck SCC (ORs 3.3, 3.0, 2.0, 4.5. 3.8, 8.4, 1.4, respectively; p<0.05) and with microsatellite instability status in only clinically relevant tumor types (gastric adenocarcinoma, colorectal adenocarcinoma, uterine endometrial adenocarcinoma, esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma (OR: 5.2, 1.9, 3.2, 3.7 and 6.5, respectively; p<0.05)). Conversely, CN changes were not significantly correlated with tumor mutational burden in almost all the tumor types.
CN changes and PD-L1 expression were highly correlated in multiple tumor types. These prevalence data on CN changes across a large cohort of different solid tumors can be used to design future clinical studies to assess whether CN changes could be a potential biomarker for ICPI.
多项研究表明，临床结果数据支持将拷贝数（CN）增益和/或丢失作为免疫检查点抑制剂（ICPI）的生物标志物。在这里，我们展示了大量实体瘤病例中 CN 变化的情况，并通过免疫组织化学分析将其与 PD-L1 蛋白表达相关联。
我们分析了 2014 年 8 月至 2020 年 6 月期间在 Foundation Medicine 进行全面基因组分析（CGP）检测的所有病例。在有食品和药物管理局批准的伴随诊断（CDx）适应证的肿瘤类型中，CN 变化与 PD-L1 表达相关，并且使用 CDx 检测来评估 PD-L1 表达。
在总共 290 种实体瘤类型的 244584 个样本中，有 17.6%（42983/244584）有 CN 增益（>标本倍性），44.6%（108970/244584）为 CN 中性，37.9%（92631/244584）有 CN 丢失。使用不同的 CN 截止值来定义阳性会导致不同的患病率估计：倍性+1，17.4%（42636/244584）；倍性+2，6.2%（15183/244584）；倍性+3，2.2%（5375/244584）；倍性+4，1.1%（2712/244584）；倍性+8，0.2%（434/244584）。CN 变化和 CN 阳性的患病率因肿瘤类型而异。在非小细胞肺癌、尿路上皮癌、乳腺癌、宫颈癌、食管鳞状细胞癌（SCC）和头颈部 SCC 中，CN 增益与 PD-L1 阳性显著相关（OR 分别为 3.3、3.0、2.0、4.5、3.8、8.4、1.4；p<0.05），并且仅在临床相关肿瘤类型中与微卫星不稳定性状态相关（胃腺癌、结直肠癌、子宫内膜腺癌、食管腺癌和胃食管交界处腺癌；OR 分别为 5.2、1.9、3.2、3.7、6.5；p<0.05）。相反，在几乎所有肿瘤类型中，CN 变化与肿瘤突变负担均无显著相关性。
CN 变化与多种肿瘤类型中的 PD-L1 表达高度相关。这些在大量不同实体瘤患者中观察到的 CN 变化的患病率数据可用于设计未来的临床研究，以评估 CN 变化是否可能成为 ICPI 的潜在生物标志物。
