Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis.
Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis.
复制标题
DOI：
--
复制
发表时间：
1994-01
期刊：
影响因子：
11.2
通讯作者：
D. Shin;Jhingook Kim;J. Ro;Jason Hittelman;J. Roth;W. Hong;W. Hittelman
中科院分区：
文献类型：
--
作者：
D. Shin;Jhingook Kim;J. Ro;Jason Hittelman;J. Roth;W. Hong;W. Hittelman
为了在头颈部癌发展的多步骤过程中确定一个潜在的中间生物标志物，我们对33例头颈部鳞状细胞癌患者的p53表达进行了免疫组化分析，这些患者的组织切片含有邻近的正常上皮、增生和/或发育不良病变。33例（45%）头颈部鳞状细胞癌中有15例表达p53，但4例正常对照患者（无癌不吸烟者）的口腔粘膜标本中均未检测到p53。为了确定头颈部肿瘤发生过程中p53表达的起始时间，我们检查了肿瘤附近的正常和癌前病变。5/24例（21%）肿瘤旁正常上皮样本、7/24例（29%）增生样本和9/20例（45%）异型增生样本表达p53。定量图像分析表明，不仅逐渐增加的组织异常的进展，但表达的拓扑变化的p53表达量。而p53的表达，当存在时，仅限于基底层在正常上皮肿瘤附近，p53的表达扩展到副基底层和浅表层的增生和不典型增生。我们的结论是，p53的表达可以改变在非常早期阶段的头部和颈部肿瘤。因此，它可能是一个很好的候选人进行风险评估，并可能作为一个中间生物标志物在化学预防试验。
With the goal of identifying a potential intermediate biomarker in the multistep process of head and neck cancer development, we conducted immunohistochemical analyses for p53 expression in 33 patients with head and neck squamous cell carcinomas whose tissue sections contained adjacent normal epithelium, hyperplastic, and/or dysplastic lesions. Fifteen of 33 (45%) squamous cell carcinomas of the head and neck expressed p53, but none of four normal control patients (cancer-free nonsmokers) expressed detectable p53 in oral mucosa specimens. To determine when p53 expression is initiated during head and neck tumorigenesis, we examined the normal and premalignant lesions adjacent to the tumors. Five of 24 (21%) samples of normal epithelium adjacent to tumors, 7 of 24 (29%) samples of hyperplasia, and 9 of 20 (45%) samples of dysplasia expressed p53. Quantitative image analysis demonstrated not only a gradual increase in the amount of p53 expression as tissue abnormalities progressed but also a topological change in expression. Whereas p53 expression, when present, was limited to the basal layer in normal epithelium adjacent to tumor, the expression of p53 expanded into the parabasal and superficial layers in hyperplasia and dysplasia. We conclude that p53 expression can be altered in very early phases of head and neck tumorigenesis. Thus, it may be an excellent candidate for risk assessment and may serve as an intermediate biomarker in chemoprevention trials.