Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival
Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival
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DOI：
10.1093/jnci/90.11.824
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发表时间：
1998-06-03
影响因子：
10.3
通讯作者：
Tweardy, DJ
中科院分区：
文献类型：
--
作者：
Grandis, JR;Melhem, MF;Tweardy, DJ
背景资料：目前，头颈部鳞状细胞癌患者复发的最准确预测因素是区域淋巴结转移的程度，因为表皮生长因子受体（EGFR）及其配体转化生长因子-α水平升高。在头颈部鳞状细胞癌患者的原发性肿瘤中检测到TGF-α，我们确定这些蛋白质的肿瘤水平是否具有预后重要性。研究方法：对EGFR和TGF-α特异的单克隆抗体用于免疫组织化学检测来自91名通过手术切除治疗的患者的原发性肿瘤的组织切片中的每种蛋白质。免疫反应性EGFR和TGF-α的水平通过使用计算机化图像分析系统来定量，并标准化为适当的标准。对数秩检验和比例风险回归分析用于计算EGFR和TGF-α水平与无病生存期相关的概率（即，没有癌症复发）和原因特异性存活（即，患者不会死于疾病）。所有P值均为双侧。结果如下：当EGFR或TGF-α的肿瘤水平作为连续变量进行分析时，EGFR水平较高的患者的无病生存率和病因特异性生存率降低（均P = .0001）或TGF-α在多变量分析中，肿瘤部位、肿瘤EGFR水平和肿瘤TGF-ar水平是无病生存的统计学显著预测因素;在一项类似分析中，局部淋巴结分期和肿瘤EGFR和TGF-α水平是病因特异性生存的重要预测因子。结论：在原发性头颈部鳞状细胞癌中EGFR和TGF-α蛋白水平的定量可能有助于识别肿瘤复发高风险患者亚组和指导治疗。
Background: The most accurate predictor of disease recurrence in patients treated for head and neck squamous cell carcinoma is, at present, the extent of regional lymph node metastasis, Since elevated levels of epidermal growth factor receptor (EGFR) and of its ligand, transforming growth factor-alpha. (TGF-alpha), have been detected in primary tumors of patients with head and neck squamous cell carcinoma, we determined whether tumor levels of these proteins were of prognostic importance. Methods: Monoclonal antibodies specific for EGFR and TGF-alpha were used for immunohistochemical detection of each protein in tissue sections of primary tumors from 91 patients who were treated by surgical resection, Levels of immunoreactive EGFR and TGF-alpha were quantified by use of a computerized image analysis system and were normalized to appropriate standards. The logrank test and proportional hazards regression analysis were used to calculate the probability that EGFR and TGF-alpha levels were associated with disease-free survival(i.e., no recurrence of cancer) and cause-specific survival (i.e., patients do not die of their disease). All P values were two-sided. Results: When tumor levels of EGFR or TGF-alpha were analyzed as continuous variables, disease-free survival and cause-specific survival were reduced among patients with higher levels of EGFR (both P = .0001) or TGF-alpha (both P = .0001), In a multivariate analysis, tumor site, tumor level of EGFR, and tumor level of TGF-ar were statistically significant predictors of disease-free survival; in a similar analysis, regional lymph node stage and tumor levels of EGFR and of TGF-alpha were significant predictors of cause-specific survival. Conclusion: Quantitation of EGFR and TGF-alpha protein levels in primary head and neck squamous cell carcinomas may be useful in identifying subgroups of patients at high risk of tumor recurrence and in guiding therapy.