头颈部鳞状细胞癌放射敏感性的生物学预测因子。
Biological predictors of radiosensitivity in head and neck squamous cell carcinoma.
机构信息
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Institute of Pathology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
出版信息
Clin Oral Investig. 2018 Jan;22(1):189-200. doi: 10.1007/s00784-017-2099-x. Epub 2017 Mar 18.
OBJECTIVES
The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation.
MATERIAL AND METHODS
The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed.
RESULTS
Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis.
CONCLUSIONS
P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation.
CLINICAL RELEVANCE
The findings may improve patient-specific therapy according to individual tumor characteristics.
目的
本研究旨在探讨预后生物标志物对接受根治性（放化疗）的晚期头颈部鳞状细胞癌患者的放射敏感性和生存的影响。
材料和方法
分析了 82 例经原发（放化疗）治疗的头颈部鳞状细胞癌患者的临床病理数据和 p16、c-Met、生存素、PD-1 和 PD-L1 的免疫组织化学染色。评估了与局部和区域性放射反应、总生存（OS）、无病生存（DFS）和疾病特异性生存（DSS）的相关性。
结果
完全肿瘤反应与患者年龄增加（p=0.007）、N0 状态（p=0.022）、M0 状态（p=0.007）和 p16 阳性（p=0.022）相关。高 PD-L1 与 M0 状态（p=0.026）相关，并提示肿瘤对放疗有反应（p=0.057）；生存素表达显示出更高的反应失败率（p=0.073）。低 PD-1 与 T 分期增加（p=0.029）和局部复发（p=0.014）相关。高 PD-1 与 PD-L1 阳性肿瘤浸润淋巴细胞呈强相关性（p<0.001）。低 PD-L1 与高 c-Met 表达呈显著相关性（p=0.01）。单因素生存分析中，无有利预后的显著预测因子包括不完全肿瘤反应（DSS，p<0.001）、单纯放疗（DSS，p=0.002）、M1 状态（DSS，p<0.001）、放射剂量降低（DSS，p=0.014）、生存素升高（DSS，p=0.045）和 c-Met 升高（OS，p<0.05）。多因素生存分析中，生存素和 c-Met 也具有预后意义。
结论
p16 和 PD-L1 提示放射敏感性，而生存素和 c-Met 提示原发性（放化疗）头颈部鳞状细胞癌的放射抵抗性。PD-1/PD-L1 免疫检查点在放射反应和生存中的作用值得进一步研究。
临床相关性
这些发现可能根据肿瘤的个体特征改善个体化治疗。
Zotero 插件