局部晚期喉癌中缺氧与增殖生物标志物与放射敏感性的关系。
The relation between hypoxia and proliferation biomarkers with radiosensitivity in locally advanced laryngeal cancer.
机构信息
Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9723 GZ, Groningen, The Netherlands.
出版信息
Eur Arch Otorhinolaryngol. 2023 Aug;280(8):3801-3809. doi: 10.1007/s00405-023-07951-9. Epub 2023 Apr 8.
PURPOSE
Treatment decision-making in advanced-stage laryngeal squamous cell carcinoma (LSCC) is difficult due to the high recurrence rates and the desire to preserve laryngeal functions. New predictive markers for radiosensitivity are needed to facilitate treatment choices. In early stage glottic LSCC treated with primary radiotherapy, expression of hypoxia (HIF-1α and CA-IX) and proliferation (Ki-67) tumour markers showed prognostic value for local control. The objective of this study is to examine the prognostic value of tumour markers for hypoxia and proliferation on locoregional recurrent disease and disease-specific mortality in a well-defined cohort of patients with locally advanced LSCC treated with primary, curatively intended radiotherapy.
METHODS
In pre-treatment biopsy tissues from a homogeneous cohort of 61 patients with advanced stage (T3-T4, M0) LSCC primarily treated with radiotherapy, expression of HIF-1α, CA-IX and Ki-67 was evaluated with immunohistochemistry. Demographic data (age and sex) and clinical data (T- and N-status) were retrospectively collected from the medical records. Cox regression analysis was performed to assess the relation between marker expression, demographic and clinical data, and locoregional recurrence and disease-specific mortality.
RESULTS
Patients with high expression of HIF-1α developed significantly more often a locoregional recurrence (39%) compared to patients with a low expression (21%) (p = 0.002). The expression of CA-IX and Ki-67 showed no association with locoregional recurrent disease. HIF-1α, CA-IX and Ki-67 were not significantly related to disease-specific mortality. Clinical N-status was an independent predictor of recurrent disease (p < 0.001) and disease-specific mortality (p = 0.003). Age, sex and T-status were not related to locoregional recurrent disease or disease-specific mortality.
CONCLUSION
HIF-1α overexpression and the presence of regional lymph node metastases at diagnosis were independent predictors of locoregional recurrent disease after primary treatment with curatively intended radiotherapy in patients with locally advanced LSCC.
目的
由于晚期喉鳞状细胞癌（LSCC）的复发率较高，且人们希望保留喉功能，因此治疗决策颇具难度。需要新的放射敏感性预测标志物来辅助治疗选择。在接受根治性放疗的早期声门型 LSCC 患者中，缺氧（HIF-1α 和 CA-IX）和增殖（Ki-67）肿瘤标志物的表达对局部控制具有预后价值。本研究旨在检查在接受根治性放疗的局部晚期 LSCC 患者中，肿瘤标志物对缺氧和增殖与局部区域复发疾病和疾病特异性死亡率的预后价值。
方法
在 61 例接受根治性放疗的局部晚期（T3-T4，M0）LSCC 患者的治疗前活检组织中，采用免疫组织化学法评估 HIF-1α、CA-IX 和 Ki-67 的表达。从病历中回顾性收集人口统计学数据（年龄和性别）和临床数据（T 分期和 N 分期）。采用 Cox 回归分析评估标志物表达、人口统计学和临床数据与局部区域复发和疾病特异性死亡率之间的关系。
结果
高 HIF-1α 表达的患者局部复发的发生率明显高于低 HIF-1α 表达的患者（39% vs. 21%）（p=0.002）。CA-IX 和 Ki-67 的表达与局部区域复发疾病无关。HIF-1α、CA-IX 和 Ki-67 与疾病特异性死亡率无显著相关性。临床 N 分期是局部复发疾病（p<0.001）和疾病特异性死亡率（p=0.003）的独立预测因素。年龄、性别和 T 分期与局部区域复发疾病或疾病特异性死亡率无关。
结论
在接受根治性放疗的局部晚期 LSCC 患者中，HIF-1α 过表达和诊断时存在区域淋巴结转移是局部区域复发疾病的独立预测因素。
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