Onur Dülger, İlhan Yaylım, Büge Öz
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Department of Pathology, Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
Indian J Pathol Microbiol. 2025 Jan 1;68(1):36-41. doi: 10.4103/ijpm.ijpm_939_23. Epub 2024 Jun 20.
Driver mutations and immunological expressions have gained importance in recent years for targeted therapies and immunotherapies of nonsmall cell lung cancer (NSCLC).
This study examined the association between PD-L1 expression and ALK , ROS1 , and EGFR driver oncogene mutations in patients with NSCLC.
A total of 501 NSCLC patients were included for analysis. Immunohistochemistry was performed with a PD-L1 clone 22c3. EGFR mutations were detected by PCR. ALK and ROS1 rearrangement analysis was performed with FISH. Results: There was a highly statistically significant difference between PD-L1 expression and EGFR mutation. PD-L1 expression was higher in the EGFR wild-type than in mutated EGFR ( P = 0.0002). There was no relationship between PD-L1 expression and ALK and ROS1 mutations ( P = 0.8899, P = 0.2512, respectively). PD-L1 expression was higher in nonadenocarcinomas (non-AC) than in adenocarcinomas (AC) ( P = 0.0438). The ALK rearrangement and EGFR mutations were higher in ACs ( P = 0.0073, P = 0.0012, respectively). ALK , ROS1 rearrangements, and EGFR mutations were higher in nonsmokers ( P < 0.05). EGFR mutations were detected more frequently in females than males ( P = 0.001). There was no relationship between gender and ALK , ROS1 , and PD-L1 ( P > 0.05). The prevalence of EGFR , ALK , and ROS1 driver mutations in the Turkish population was 9.3%, 5.3%, and 2.4%, respectively.
In conclusion, PD-L1 expression and mutated EGFR status have a highly negative association. PD-L1 expression was higher in EGFR wild-type patients. Therefore, it shows that the opportunity to receive PD-L1-related treatment may be higher in these patients. We think that PD-L1 immunohistochemical evaluation will increase the clinical predictive importance in EGFR wild-type cases.
近年来,驱动基因突变和免疫表达在非小细胞肺癌(NSCLC)的靶向治疗和免疫治疗中变得愈发重要。
本研究探讨了NSCLC患者中PD-L1表达与ALK、ROS1和EGFR驱动癌基因突变之间的关联。
共纳入501例NSCLC患者进行分析。采用PD-L1克隆22c3进行免疫组织化学检测。通过PCR检测EGFR突变。采用荧光原位杂交(FISH)进行ALK和ROS1重排分析。结果:PD-L1表达与EGFR突变之间存在高度统计学显著差异。EGFR野生型中的PD-L1表达高于EGFR突变型(P = 0.0002)。PD-L1表达与ALK和ROS1突变之间无相关性(分别为P = 0.8899,P = 0.2512)。非腺癌(non-AC)中的PD-L1表达高于腺癌(AC)(P = 0.0438)。AC中的ALK重排和EGFR突变更高(分别为P = 0.0073,P = 0.0012)。非吸烟者中的ALK、ROS1重排和EGFR突变更高(P < 0.05)。女性中EGFR突变的检测频率高于男性(P = 0.001)。性别与ALK、ROS1和PD-L1之间无相关性(P > 0.05)。土耳其人群中EGFR、ALK和ROS1驱动基因突变的发生率分别为9.3%、5.3%和2.4%。
总之,PD-L1表达与突变的EGFR状态呈高度负相关。EGFR野生型患者的PD-L1表达更高。因此,表明这些患者接受PD-L1相关治疗的机会可能更高。我们认为PD-L1免疫组织化学评估将增加EGFR野生型病例的临床预测重要性。