SMALL SUBGROUP OF AGGRESSIVE, HIGHLY PROLIFERATIVE PROSTATIC CARCINOMAS DEFINED BY P53 ACCUMULATION
SMALL SUBGROUP OF AGGRESSIVE, HIGHLY PROLIFERATIVE PROSTATIC CARCINOMAS DEFINED BY P53 ACCUMULATION
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DOI：
10.1093/jnci/84.11.883
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发表时间：
1992-06-03
期刊：
影响因子：
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通讯作者：
ISOLA, J
中科院分区：
文献类型：
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作者：
VISAKORPI, T;KALLIONIEMI, OP;ISOLA, J
背景资料：在多种人类恶性肿瘤中发现了p53基因突变，导致半衰期延长的改变的p53蛋白积聚。目的：探讨p53蛋白在前列腺癌中的表达及意义。方法：材料包括137例石蜡包埋的原发性前列腺癌。使用多克隆p53特异性CM-1抗体通过免疫组织化学染色研究p53蛋白的积累。增殖活性通过DNA流式细胞术和使用单克隆PC 10抗体的增殖细胞核抗原（PCNA）的免疫组化检测来确定。结果如下：8例（6%）肿瘤中超过20%的肿瘤细胞显示出强烈的p53染色，15例（11%）仅具有较低水平的免疫反应性，114例（83%）显示无染色。高水平p53积聚与高组织学分级（P <0.001）、DNA异倍体（P <0.05）和高细胞增殖率（通过流式细胞术S期分析（P <0.01）或PCNA表达（P <0.01）定义）相关。高水平的p53积累预示着短的无进展间隔（P < .01）和较差的生存率（P < .001），与p53阴性病例相比，死亡的相对风险约为12倍。低水平的p53积累没有预后意义。结论：p53的积累赋予前列腺癌细胞增殖优势，并定义了高度恶性癌的一个小亚组。
Background: Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. Purpose: We studied the significance of p53 protein accumulation in prostatic carcinoma. Methods: The material consisted of 137 paraffin-embedded, primary prostatic carcinomas. Accumulation of p53 protein was studied by immunohistochemical staining using a Polyclonal p53-specific CM-1 antibody. Proliferation activity was determined by DNA flow cytometry and by immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using a monoclonal PC10 antibody. Results: Eight (6%) of the tumors showed intense p53 staining in more than 20% of the tumor cells, 15 (11%) had only lower level immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation was associated with high histologic grade (P < .001), DNA aneuploidy (P < .05), and high cell proliferation rate as defined by flow cytometric S-phase analysis (P < .01) or PCNA expression (P < .01). High-level p53 accumulation predicted short, progression-free interval (P < .01) and poor survival (P < .001), with about a 12-fold relative risk of death as compared with p53-negative cases. Low-level p53 accumulation had no prognostic significance. Conclusions: Accumulation of p53 confers proliferative advantage for prostatic carcinoma cells and defines a small subgroup of highly malignant carcinomas.