Tissue Culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
Surgical Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
J Egypt Natl Canc Inst. 2022 May 30;34(1):23. doi: 10.1186/s43046-022-00121-8.
Programmed death ligand-1 (PD-L1), anaplastic lymphoma kinase (ALK), and c-ros oncogene1 (ROS1) expression may influence the prognosis of non-small cell lung carcinoma (NSCLC). We aimed to investigate the prognostic and predictive significance of PD-1/PD-L1 along with c-ros ROS1 and ALK in NSCLC patients.
Immunohistochemistry used to identify ALK, ROS1, PD-1, and PD-L1 proteins expression as well as ROS1 rearrangement via fluorescence in situ hybridization, in 70 NSCLC patients. Results were related to clinicopathological feature, survival, and treatment response.
Expression of ROS1, ALK, PD-1, and PD-L1 and ROS1-rearrangement were detected in 18.57%, 54.29%, 84.29%, 87.14%, and 15.71% of the cases, respectively. No association was found between ROS1, PD-1, and PD-L1 and any clinicopathological features, survival, or treatment outcome. ALK expression significantly associated with stage-IV and left-sided tumors. Epidermal growth factor receptor (EGFR) mutation and ALK-positive patients had significantly reduced progression-free survival than patients with wild type EGFR [HR: 1.99, 95% CI: 1.37-2.93, p < 0.001] and negative-ALK expression [HR: 1.46, 95% CI: 1.03-2.07, p = 0.03]. In multivariate analysis, lymph node metastasis, EGFR-mutations, and ALK were independent predictors of NSCLC. PD-L1 expression was significantly correlated with PD-1 but not with ROS1, ALK, or EGFR-mutation.
Positive ALK expression and EGFR-mutations are independent adverse predictors of NSCLC. Overexpression of PD-1/PD-L1 is not a significant prognostic marker in NSCLC patients receiving chemotherapy, making them susceptible to immunotherapy. Since PD-1/PD-L1 expression is independent to oncogenic driver mutations, future studies into specific immune checkpoint inhibitors combined with targeted therapies for individualized treatment of NSCLC is warranted. Positive ALK expression and EGFR mutations are independent risk factors for NSCLC. Overexpression of PD-1/PD-L1 is not a significant prognostic factor in patients with NSCLC who are receiving chemotherapy, making them immunotherapy susceptible. Given that PD-1/PD-L1 expression is not dependent on oncogenic driver mutations, additional research into specific immune checkpoint inhibitors in combination with targeted therapies for the treatment of NSCLC on an individual basis is warranted.
程序性死亡配体 1（PD-L1）、间变性淋巴瘤激酶（ALK）和 c-ros 原癌基因 1（ROS1）的表达可能影响非小细胞肺癌（NSCLC）的预后。我们旨在研究 PD-1/PD-L1 以及 c-ros ROS1 和 ALK 在 NSCLC 患者中的预后和预测意义。
通过免疫组织化学检测 70 例 NSCLC 患者中 ALK、ROS1、PD-1 和 PD-L1 蛋白的表达以及 ROS1 重排，通过荧光原位杂交进行检测。结果与临床病理特征、生存和治疗反应相关。
ROS1、ALK、PD-1 和 PD-L1 的表达以及 ROS1 重排分别在 18.57%、54.29%、84.29%、87.14%和 15.71%的病例中检测到。ROS1、PD-1 和 PD-L1 与任何临床病理特征、生存或治疗结果均无关联。ALK 表达与 IV 期和左侧肿瘤显著相关。与野生型 EGFR 相比，表皮生长因子受体（EGFR）突变和 ALK 阳性患者的无进展生存期明显缩短[风险比（HR）：1.99，95%可信区间（CI）：1.37-2.93，p<0.001]和阴性-ALK 表达[HR：1.46，95%CI：1.03-2.07，p=0.03]。多变量分析显示，淋巴结转移、EGFR 突变和 ALK 是 NSCLC 的独立预测因子。PD-L1 表达与 PD-1 显著相关，但与 ROS1、ALK 或 EGFR 突变不相关。
ALK 阳性表达和 EGFR 突变是 NSCLC 的独立不良预后因素。PD-1/PD-L1 的过表达不是接受化疗的 NSCLC 患者的显著预后标志物，使他们易受免疫治疗影响。由于 PD-1/PD-L1 的表达与致癌驱动突变无关，因此有必要对 NSCLC 患者进行特定免疫检查点抑制剂联合靶向治疗的个体化治疗进行进一步研究。ALK 阳性表达和 EGFR 突变是 NSCLC 的独立危险因素。PD-1/PD-L1 的过表达不是接受化疗的 NSCLC 患者的显著预后标志物，使他们易受免疫治疗影响。鉴于 PD-1/PD-L1 的表达不依赖于致癌驱动突变，因此有必要对针对 NSCLC 的特定免疫检查点抑制剂联合靶向治疗进行进一步研究。
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