a 1st Department of Pathology and Experimental Cancer Research , Semmelweis University , Budapest , Hungary.
b 2nd Department of Pathology, MTA-SE NAP Brain Metastasis Research Group Hungarian Academy of Sciences , Semmelweis University , Budapest , Hungary.
Acta Oncol. 2019 Aug;58(8):1087-1094. doi: 10.1080/0284186X.2019.1598575. Epub 2019 Apr 19.
Predictive biomarkers for immunotherapy in lung cancer are intensively investigated; however, correlations between PD-L1/PD-1 expressions and clinical features or histopathological tumor characteristics determined on hematoxylin and eosin stained sections have not extensively been studied. We determined PD-L1 expression of tumor cells (TC) and immune cells (IC), and PD-1 expression of IC by immunohistochemistry in 268 lung adenocarcinoma (LADC) patients, and correlated the data with smoking, COPD, tumor grade, necrosis, lepidic growth pattern, vascular invasion, density of stromal IC, and status of the tumors. There was a positive correlation between PD-L1 expression of TC and IC, as well as PD-L1 and PD-1 expression of IC. Tumor necrosis was associated with higher PD-L1 expression of TC and PD-1 expression of IC. A negative correlation was observed between lepidic growth pattern and PD-L1 expression of TC and PD-L1/PD-1 expression of IC. mutation seemed to negatively correlate with PD-1 expression of IC, but this tendency could not be verified when applying corrections for multiple comparisons. No significant effect of the mutation on any of the studied variables could be established. Here we first demonstrate that the presence of necrosis correlates with higher PD-L1 expression of TC and PD-1 expression of IC in LADC. Further studies are required to determine the predictive value of this observation in LADC patients receiving immunotherapy.
我们在 268 例肺腺癌(LADC)患者中通过免疫组织化学法测定了肿瘤细胞(TC)和免疫细胞(IC)的 PD-L1 表达以及 IC 的 PD-1 表达,并将这些数据与吸烟、COPD、肿瘤分级、坏死、贴壁生长模式、血管侵犯、间质 IC 密度以及 状态相关联。TC 和 IC 的 PD-L1 表达以及 PD-L1 和 IC 的 PD-1 表达之间存在正相关。肿瘤坏死与 TC 的 PD-L1 表达和 IC 的 PD-1 表达升高相关。我们观察到贴壁生长模式与 TC 的 PD-L1 表达和 IC 的 PD-L1/PD-1 表达呈负相关。 突变似乎与 IC 的 PD-1 表达呈负相关,但在进行多次比较校正后,这种趋势无法得到验证。 突变对研究的任何变量均无显著影响。 在这里,我们首次证明坏死的存在与 LADC 中 TC 的 PD-L1 表达和 IC 的 PD-1 表达升高相关。需要进一步的研究来确定在接受免疫治疗的 LADC 患者中观察到这一现象的预测价值。