Combined and sequential expression of p53, Rb, Ras and Bcl-2 in bronchial preneoplastic lesions
Combined and sequential expression of p53, Rb, Ras and Bcl-2 in bronchial preneoplastic lesions
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DOI：
10.1177/030089169708300222
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发表时间：
1997-03-01
期刊：
影响因子：
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通讯作者：
Nenci, I
中科院分区：
文献类型：
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作者：
Ferron, PE;Bagni, I;Nenci, I
目的和背景：在支气管癌前病变中已经检测到几种简单的分子异常，但是这些改变同时存在的情况很少被研究。研究方法：我们研究了，通过免疫组化方法，p53，Rb，Ras和Bcl-2的表达在65例样本中的手术标本和诊断活检选择的支气管上皮癌前病变的存在。为了分析相同区域中所有标志物的组合表达，我们准确地绘制了进行免疫组织化学反应的每个连续切片，将每个标本细分为25 x显微镜视野，这允许良好的地形图绘制。结果如下：结果发现，p53阳性和Rb阴性的显微镜视野的频率与病变的形态学分级直接相关。另一方面，Ras表达表征不显示鳞状分化的高级别病变（非鳞状Cis）。关于Bcl-2的表达，只有轻微的差异，阳性分布之间的不同病变。更有趣的是在相同区域的所有标记物的平行评估：发现与组织病理学特征的严重程度相关的主要模式之一是以组合的p53高表达/Rb低表达为特征;此外，当Ras和Bcl-2高表达与上述模式叠加时，前者主要表现为非鳞状Cis，而后者仅存在于高级别鳞状病变中。然而，最常见的模式并没有显示任何改变的研究标志物，这表明其他机制可能参与支气管癌的发生。结论：在支气管癌前病变中联合检测分子异常可以阐明肺癌发生的步骤;此外，一种简单而廉价的方法，如免疫组化，也可以常规应用于细胞学标本，以检测那些病变或患者，这些病变或患者容易进展为肺癌。
Aims and background: Several simple molecular abnormalities have been detected rn bronchial preneoplastic lesions, but the simultaneous presence of these alterations has been scarcely investigated. Methods: We studied, by an immunohistochemical method, the expression of p53, Rb, Ras and Bcl-2 in 65 samples from surgical specimens and diagnostic biopsies selected for the presence of preneoplastic changes in the bronchial epithelium. To perform an analysis of the combined expression of all markers in the same areas, we accurately mapped every consecutive section on which immunohistochemical reactions were performed, subdividing each specimen into 25x microscopic fields, which allowed good topographical mapping. Results: It was found that the frequency of p53-positive and Rb-negative microscopic fields was directly related to the morphological grading of lesions. On the other hand, Ras expression characterized high-grade lesions not Showing squamous differentiation (non-squamous Cis). Regarding Bcl-2 expression, only slight differences in positivity distribution were found between the different lesions. More interesting was the parallel evaluation of all markers in the same areas: one of the main patterns, found to be correlated with the severity of histopathological features, was characterized by combined p53 hyperexpression/Rb hypoexpression; furthermore, when Ras and Bcl-2 hyperexpression were superimposed to the above pattern, the former mainly characterized non-squamous Cis, while the latter was present only in high-grade squamous lesions. However, the most frequently encountered pattern did not show any alteration of the studied markers, suggesting that other mechanisms could be involved in bronchial carcinogenesis. Conclusions: The detection of combined molecular abnormalities in bronchial preneoplasia could clarify the steps involved in lung carcinogenesis; furthermore, a simple and inexpensive method, such as immunohistochemistry, could be routinely applied also to cytologic specimens in order to detect those lesions, or patients, that are prone to progression towards lung cancer.