Asynchronous modulation of transforming growth factor alpha and epidermal growth factor receptor protein expression in progression of premalignant lesions to head and neck squamous cell carcinoma.
Asynchronous modulation of transforming growth factor alpha and epidermal growth factor receptor protein expression in progression of premalignant lesions to head and neck squamous cell carcinoma.
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发表时间：
1998
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通讯作者：
J. Rubin Grandis;D. Tweardy;M. Melhem
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作者：
J. Rubin Grandis;D. Tweardy;M. Melhem
头颈部鳞状细胞癌的发生是上呼吸消化道粘膜基因型和表型改变累积的结果。表皮生长因子受体（EGFR）及其配体转化生长因子α（TGF-α）的上调先前已被确定为头颈癌发生的早期事件。为了确定在头颈部癌症发展中TGF-α和EGFR蛋白表达增加的时间，我们检查了来自三个不同且互补的患者组的进行性粘膜异型增生：（a）来自病变显示不同程度异型增生的患者的样本（n = 22）与来自性别和年龄匹配的对照组的粘膜样本（n = 8）相比;（B）在单个时间点具有表现出不同程度的异型增生的病变的患者（n = 3）;和（c）在异型增生部位经过数年进展为浸润性癌症的患者（n = 7）。免疫组织化学分析与TGF-α和EGFR的特异性单克隆抗体用于检测蛋白表达在所有标本。使用计算机图像分析系统进一步定量蛋白质水平。在所有三组中，我们发现TGF-α蛋白水平在轻度不典型增生中比对照正常粘膜升高，并且不随不典型增生程度的增加而进一步调节。相比之下，EGFR水平在轻度异型增生中相对较低，并且随着异型增生程度的增加而增加。这些发现表明，在头颈部鳞状细胞癌的发病机制中，TGF-α和EGFR的上调在时间上和机制上都是不同的事件。
The development of head and neck squamous cell carcinoma occurs as a result of the accumulation of genotypic and phenotypic alterations in the upper aerodigestive tract mucosa. Up-regulation of epidermal growth factor receptor (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), have been identified previously as early events in head and neck carcinogenesis. To determine the timing of increased TGF-alpha and EGFR protein expression in the development of head and neck cancer, we examined progressive mucosal dysplasias from three distinct and complimentary patient groups: (a) samples from patients with lesions demonstrating different degrees of dysplasia (n = 22) compared with mucosa samples from gender and age-matched controls (n = 8); (b) patients with lesions demonstrating different degrees of dysplasia at a single time point (n = 3); and (c) patients who progressed over several years to invasive cancer at the site of dysplasia (n = 7). Immunohistochemical analysis with monoclonal antibodies specific for TGF-alpha and EGFR were used to detect protein expression in all specimens. Protein levels were further quantitated using a computerized image analysis system. In all three groups, we found that TGF-alpha protein levels were elevated in mild dysplasia compared with control normal mucosa and were not further modulated with increasing degrees of dysplasia. In contrast, EGFR levels were relatively low in mild dysplasia and increased with higher degrees of dysplasia. These findings indicate that up-regulation of TGF-alpha and EGFR are distinct events both chronologically and, possibly, mechanistically in the pathogenesis of head and neck squamous cell carcinoma.