外阴鳞癌中 PD-L1 和 PD-1 表达的临床影响。
Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva.
机构信息
Department of Obstetrics and Gynaecology, Medical Faculty, University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931, Cologne, Germany.
Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Straße 62, 50937, Cologne, Germany.
出版信息
J Cancer Res Clin Oncol. 2019 Jun;145(6):1651-1660. doi: 10.1007/s00432-019-02915-1. Epub 2019 Apr 10.
PURPOSE
Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value.
METHODS
Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test.
RESULTS
PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001).
CONCLUSION
The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.
目的
外阴鳞状细胞癌（SQCV）是女性中第五种最常见的癌症，占女性所有生殖器癌症的 5%左右。PD-L1 信号通路在许多恶性肿瘤中被激活，其阻断可增强抗肿瘤免疫。我们研究的目的是检查外阴鳞状细胞癌中 PD-L1 和 PD-1 的蛋白表达，及其与临床病理特征的相关性和预后价值。
方法
对一家机构治疗的 SQCV 患者进行分析。使用 28-8 抗体对各自的 FFPE 组织块的 4μm 厚切片进行 PD-L1 免疫组化染色。分别对肿瘤细胞（TC）和肿瘤相关免疫细胞进行 PD-L1 评分。提取 DNA 以确定 HPV 状态。使用 Kaplan-Meier 估计无病生存率和总生存率，并通过对数秩检验进行比较。
结果
在 32.9%的患者中可以观察到肿瘤细胞中 PD-L1 的表达。在 91.4%的患者中证实了肿瘤周围免疫细胞中 PD-L1 的表达。在肿瘤细胞中 PD-L1 的表达与肿瘤分期之间存在显著相关性（p=0.007）。PD-L1 表达与 HPV 状态无关。使用对数秩检验，我们不能证明无病生存率（p=0.434）和总生存率（p=0.858）有任何显著差异。回归分析表明，淋巴结状态是生存的预测因素（p<0.001）。
结论
本研究表明，相当数量的外阴鳞状细胞癌患者的 TC 和肿瘤相关免疫细胞中均表达 PD-L1。此外，TC 中 PD-L1 表达与肿瘤分期的显著相关性表明 PD-L1 表达在肿瘤发展过程中的临床意义。这些数据表明，SQCV 可能对免疫检查点抑制敏感，为未来的临床试验提供了合理依据。
Zotero 插件