Rubin Grandis J, Melhem M F, Gooding W E, Day R, Holst V A, Wagener M M, Drenning S D, Tweardy D J
Department of Otolaryngology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, PA, USA.
J Natl Cancer Inst. 1998 Jun 3;90(11):824-32. doi: 10.1093/jnci/90.11.824.
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.
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.
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-alpha 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.
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.
目前，头颈部鳞状细胞癌患者疾病复发的最准确预测指标是区域淋巴结转移的程度。由于在头颈部鳞状细胞癌患者的原发性肿瘤中已检测到表皮生长因子受体（EGFR）及其配体转化生长因子-α（TGF-α）水平升高，我们确定这些蛋白的肿瘤水平是否具有预后意义。
使用针对EGFR和TGF-α的单克隆抗体，对91例接受手术切除治疗患者的原发性肿瘤组织切片中的每种蛋白进行免疫组织化学检测。通过计算机图像分析系统对免疫反应性EGFR和TGF-α水平进行定量，并将其标准化至适当标准。采用对数秩检验和比例风险回归分析来计算EGFR和TGF-α水平与无病生存期（即癌症未复发）和病因特异性生存期（即患者不因疾病死亡）相关的概率。所有P值均为双侧。
当将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（P均 = 0.0001）或TGF-α水平较高（P均 = 0.0001）的患者无病生存期和病因特异性生存期均缩短。在多变量分析中，肿瘤部位、EGFR肿瘤水平和TGF-α肿瘤水平是无病生存期的统计学显著预测指标；在类似分析中，区域淋巴结分期以及EGFR和TGF-α的肿瘤水平是病因特异性生存期的显著预测指标。
对头颈部原发性鳞状细胞癌中EGFR和TGF-α蛋白水平进行定量，可能有助于识别肿瘤复发高危患者亚组并指导治疗。
