Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma.
Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma.
复制标题
作者：
E. Messing
为了评估尿路上皮细胞上表皮生长因子（EGF）受体（EGF-R）的分布和密度，使用针对人EGF-R结合部分的单克隆抗体对正常尿路上皮细胞（N = 20）、来自非尿路上皮泌尿系统恶性肿瘤患者（N = 15）和炎性疾病患者（N = 8）的尿路上皮细胞的冷冻标本进行免疫组织学研究，低级别浅表性移行细胞癌（TCC）（N = 13）、高级别浅表性或浸润性TCC（N = 28），以及来自膀胱其他部位（或同侧肾盂/输尿管）的低级别浅表性（N = 5）或高级别（N = 21）TCC患者的内窥镜下正常表现的尿路上皮。在95%的正常尿路上皮标本和100%的无尿路上皮恶性肿瘤的病理标本中，EGF-R仅在上皮细胞的基底层（在中间细胞上具有分散的代表性）被发现。另外，92.3%的低级别浅表TCC和100%的高级别TCC的标本在尿路上皮的浅表层和深层都有丰富的EGF-Rs表达。这种恶性分布的EGF-R也见于其他地方TCC患者的所有内镜检查正常的尿路上皮标本。EGF-Rs的密度与肿瘤的级别密切相关的“癌前病变”和坦率的肿瘤性尿路上皮。我们的结论是表皮生长因子受体的表达对尿路上皮癌前病变和恶性组织与尿EGF的相互作用。为了确定改变尿液的生理化学环境是否会干扰这种相互作用，在四种人TCC细胞系上评估了pH对EGF结合和生长反应的影响。Scatchard图表明，从5.0到7.5的pH变化并没有显著改变受体的总数，但随着每个TCC靶标中pH从7.5降低到5，EGF-R亲和力降低约20倍。类似地，在pH小于或等于7.0时，EGF在pH 7.5下的显著生长刺激被废除，而在较低pH下，在不存在EGF的情况下的生长速率保持不变。因此，似乎尿酸化可能在管理和预防复发性膀胱癌方面有希望。
To evaluate the distribution and density of epidermal growth factor (EGF) receptors (EGF-Rs) on urothelium, immunohistological studies using a monoclonal antibody to the binding portion of the human EGF-R were performed on frozen specimens of normal urothelium (N = 20), urothelium from patients with nonurothelial urological malignancies (N = 15) and inflammatory diseases (N = 8), low grade superficial transitional cell carcinomas (TCC) (N = 13), high grade superficial or invasive TCC (N = 28), and endoscopically normal appearing urothelium from patients with low grade superficial (N = 5) or high grade (N = 21) TCC elsewhere in the bladder (or ipsilateral renal pelvis/ureter). EGF-Rs are found only on the basal layer of epithelial cells (with scattered representation on intermediate cells) in 95% of normal urothelial specimens and 100% of pathological specimens without urothelial malignancy. Alternatively, 92.3% of specimens of low grade superficial TCC and 100% of high grade TCCs had EGF-Rs richly expressed on the superficial as well as the deeper layers of urothelium. This "malignant" distribution of EGF-Rs was also found on all specimens of endoscopically normal appearing urothelium in patients with TCC elsewhere. The density of EGF-Rs correlated closely with tumor grade on both "premalignant" and frankly neoplastic urothelium. We conclude that the expression of EGF-Rs on urothelium favors the interaction of premalignant and malignant tissue with urinary EGF. To determine if altering the physiochemical environment of urine could interfere with this interaction, the effects of pH on the binding of and growth responses to EGF were assessed on four human TCC cell lines. Scatchard plots demonstrated that varying pH from 5.0 to 7.5 did not significantly change the total number of receptors, but EGF-R affinity was reduced approximately 20-fold as pH decreased from 7.5 to 5 in each TCC target. Similarly, significant growth stimulation by EGF at pH 7.5 was abrogated at pH less than or equal to 7.0 while growth rates in the absence of EGF remained unchanged at lower pHs. It thus appears that urinary acidification may hold promise in the management and prevention of recurrent bladder cancer.