Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells during the development of human lung adenocarcinoma.
Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells during the development of human lung adenocarcinoma.
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发表时间：
1997
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通讯作者：
H. Hayashi;H. Miyamoto;T. Ito;Y. Kameda;N. Nakamura;Y. Kubota;H. Kitamura
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作者：
H. Hayashi;H. Miyamoto;T. Ito;Y. Kameda;N. Nakamura;Y. Kubota;H. Kitamura
我们的研究表明，周围型肺腺癌的发展主要是由几个步骤，从不典型腺瘤样增生，通过早期腺癌，以显性腺癌，和一些p53异常在这一进程中发挥了重要作用。在本研究中，我们用免疫组织化学方法检测了p53诱导的细胞周期蛋白依赖性激酶抑制剂p21 Waf 1/Cip 1（p21）在肺腺癌不同发育阶段细胞中的表达腺瘤样增生32例，早期腺癌14例，高分化腺癌23例，17例中、低分化腺癌）与19例反应性增生性病变作对照，分析p53与p21表达的关系。在正常肺支气管肺泡细胞表达很少或没有p21和没有p53的表达。不仅在反应性，但也肿瘤病变，无论其发展阶段，细胞表达p21在不同的频率。平均标记指数范围为5.4 - 13.8%，这些类别之间没有显著差异。p21在中、低分化腺癌中的表达相对较低（5.5%）与高分化腺癌相比（12.2%）和高水平p21表达者（10% <或=阳性细胞）在后一组中更常见（1/17（6%）vs 3/23（35%），P < 0.05），提示p21表达受肿瘤细胞分化程度的影响。p21和p53在反应性病变中的表达呈正相关（r = 0.88; P < 0.001），而在肿瘤性病变中的表达无相关性（-0.12 ≤ r ≤ 0.26）。这些结果表明，p21的表达依赖于p53的表达在反应性肺细胞，而p21的表达是至少部分独立的p53从最早的肺腺癌肿瘤发生的最充分发展的步骤。我们的结论是，p53依赖的细胞周期调控的中断是一个非常早期的事件在肺腺癌的肿瘤发生。
Our studies suggested that adenocarcinoma of the peripheral lung mostly develops by several steps from atypical adenomatous hyperplasia through early adenocarcinoma to overt adenocarcinoma, and that some p53 abnormalities play an important role in this progression. In the present study, we examined by immunohistochemistry the expression of p53-inducible cyclin-dependent kinase inhibitor p21Waf1/Cip1 (p21) in the cells at various developmental stages of lung adenocarcinoma (32 lesions of adenomatous hyperplasia, 14 of early adenocarcinoma, 23 of well differentiated adenocarcinoma, and 17 of moderately or poorly differentiated adenocarcinoma) in comparison with 19 reactive proliferative lesions and analyzed the relationship between p53 and p21 expression. Bronchioalveolar cells in the normal lung expressed very little or no p21 and no p53 expression. In not only reactive but also neoplastic lesions regardless of their developmental stage, the cells expressed p21 at various frequencies. The average labeling indices ranged from 5.4 to 13.8%, and there was no significant difference between any of these categories. The expression of p21, however, tended to be relatively low in moderately and poorly differentiated adenocarcinomas (5.5%) compared to well differentiated adenocarcinomas (12.2%), and high-level p21 expressors (10% < or = positive cells) were more frequent in the latter group (1 of 17 (6%) versus 3 of 23 (35%), P < 0.05), suggesting that p21 expression is affected by the degree of differentiation of the neoplastic cells. Although the correlation was positive between the expression of p21 and p53 in reactive lesions (r = 0.88; P < 0.001), none was found in neoplastic lesions at any step or grade (-0.12 < or = r < or = 0.26). These results indicated that p21 expression depends upon p53 expression in reactive lung cells, whereas p21 expression is at least in part independent of that of p53 from the earliest to the most fully developed step of lung adenocarcinoma tumorigenesis. We concluded that disruption of the p53-dependent cell cycle regulation is a very early event in the tumorigenesis of lung adenocarcinoma.