p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer.
p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer.
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发表时间：
1993-11
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通讯作者：
D. Esrig;C. Spruck;P. Nichols;B. Chaiwun;K. Steven;S. Groshen;Su‐Chiu Chen;D. Skinner;P. Jones
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作者：
D. Esrig;C. Spruck;P. Nichols;B. Chaiwun;K. Steven;S. Groshen;Su‐Chiu Chen;D. Skinner;P. Jones
采用免疫组织化学方法检测73例膀胱移行细胞癌组织中P53核聚集情况，并与单链构象多态分析(SSCP)和DNA序列分析检测的P53基因突变进行比较。免疫组织化学研究在福尔马林固定、石蜡包埋的组织切片上进行。免疫组织化学检测P53基因突变与P53核反应性之间存在高度相关(P=0.0001)。在32例SSCP检测为p53突变的肿瘤中，27例(84%)有P53核反应。在5例无P53核反应的肿瘤中，4例有外显子5的突变。而在41例分子分析未发现P53突变的肿瘤中，有12例(29%)有P53免疫反应。这表明免疫组织化学方法在检测p53突变方面可能比SSCP更敏感，或者不一致的病例代表有野生型P53蛋白积聚的肿瘤，P53基因没有突变。在15例外显子8突变的肿瘤中，13例免疫组化显示高强度均相P53核反应，所有位于第280位密码子的突变均显示高强度均一免疫反应。然而，3个外显子6突变的肿瘤中有3个肿瘤显示低水平的P53免疫反应，而6个外显子5突变的肿瘤中有4个肿瘤没有检测到P53核反应。这表明在分析P53核聚集时观察到的免疫反应的异质性可能与P53基因突变的位置有关。在54名接受了膀胱切除术的患者中，可以获得关于肿瘤分级、分期、淋巴状态、无病间隔和总生存期的信息。P53蛋白表达与肿瘤分级(P=0.003.0 5)和分期(P=0.0 1)显著相关。我们的结论是，在福尔马林固定的石蜡包埋组织中，免疫组织化学检测到的P53核聚集与P53基因的突变高度相关；这种关联现已在大量肿瘤中得到证实。P53核活性的异质性似乎与P53基因的突变部位有关。有一小部分p53基因突变的肿瘤在免疫组织化学中没有显示出可检测到的P53核聚集。此外，一小部分但相当大比例的肿瘤显示出P53核反应，但SSCP没有显示出可检测到的P53基因突变。最后，通过免疫组织化学或分子方法检测，膀胱癌的分级和分期都与P53的改变有关。
Seventy-three transitional cell carcinomas of the bladder were analyzed by immunohistochemistry for p53 nuclear accumulation, and the results were compared to mutations detected in the p53 gene by single strand conformational polymorphism analysis (SSCP) and DNA sequence analysis. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections. A highly significant association between the presence of p53 mutations and p53 nuclear reactivity as detected by immunohistochemistry was found (P = 0.0001). Of 32 tumors that demonstrated p53 mutations by SSCP, 27 (84%) showed p53 nuclear reactivity. Of the five cases that did not demonstrate p53 nuclear reactivity, four had mutations in exon 5. However, of 41 tumors with no evidence of p53 mutation by molecular analysis, 12 (29%) showed p53 immunoreactivity. This indicates that immunohistochemical methods may be more sensitive than SSCP in detecting p53 mutations or that discordant cases represent tumors with accumulation of wild type p53 protein, without mutations at the p53 locus. Of the 15 tumors that were found to have mutations at exon 8, 13 demonstrated high-intensity homogeneous p53 nuclear reactivity by immunohistochemistry, and all mutations located at codon 280 demonstrated high-intensity homogeneous immunoreactivity. However, three of three tumors with exon 6 mutations demonstrated low-level p53 immunoreactivity, and four of six tumors with mutations in exon 5 showed no detectable p53 nuclear reactivity. This indicates that the heterogeneity of immunoreactivity observed when analyzing p53 nuclear accumulation may be related to the site of the p53 gene mutation. Information on tumor grade, stage, lymph node status, disease-free interval, and overall survival were available in 54 patients who had undergone cystectomy. A significant association was observed between p53 alterations (detected by immunohistochemistry and SSCP) and histological tumor grade (P = 0.003) and stage (P = 0.01). We conclude that the immunohistochemical detection of p53 nuclear accumulation in formalin-fixed, paraffin-embedded tissue is highly associated with mutations in the p53 gene; this association has now been demonstrated in a large number of tumors. The heterogeneity of p53 nuclear reactivity seems to be related to the site of mutation in the p53 gene. A small proportion of tumors with a p53 gene mutation do not demonstrate immunohistochemically detectable p53 nuclear accumulation. Furthermore, a small but substantial proportion of tumors demonstrate p53 nuclear reactivity but do not show detectable mutations in the p53 gene by SSCP. Finally, both grade and stage of bladder cancer are related to p53 alterations, detected by immunohistochemistry or molecular methods.(ABSTRACT TRUNCATED AT 400 WORDS)