p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis.-猫眼课题宝

DOI：

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发表时间：

1997

期刊：

The American journal of pathology

影响因子：

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通讯作者：

中科院分区：

其他

文献类型：

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作者：

H. Tashiro;C. Isacson;R. Levine;R. Kurman;Kathleen R. Cho;L. Hedrick

子宫浆液性癌(USC)是一种少见的侵袭性子宫内膜癌，与疾病进展迅速和预后不良有关。免疫组织化学显示USC及其新发现的子宫内膜上皮内癌(EIC)均有较强的P53过表达，提示P53基因在其发病机制中发生了改变。在本研究中，我们使用直接序列分析对21个USCs和9个EICs进行了p53基因突变的评估，发现90%的USCs和78%的EICs存在突变。值得注意的是，在3例无相关浸润性癌的EIC中发现了突变，而在同步的USC和EIC中发现了相同的突变。大多数USCs和EICs中P53免疫反应较强，且与P53基因突变相关，尽管缺乏反应性并不总是意味着没有基因突变。染色体17p杂合性丢失在100%的USCs和43%的EICS中观察到，表明野生型p53等位基因的丢失发生在浆液性癌的早期发展中。总体而言，我们的结果显示P53突变在USC和EIC中非常常见。EIC中P53基因突变的存在进一步表明，P53基因突变在浆液性癌的早期发病机制中起重要作用，可能与其侵袭性生物学行为有关。

Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and a poor prognosis. Both USC and its recently described putative precursor, endometrial intraepithelial carcinoma (EIC), demonstrate strong p53 overexpression by immunohistochemistry, suggesting alteration of the p53 gene in their pathogenesis. In the present study, we evaluated 21 USCs and 9 EICs for mutations in the p53 gene using direct sequence analysis and found that 90% of USCs and 78% of EICs contain mutations. Significantly, mutations were found in 3 cases of EIC without associated invasive carcinoma and identical mutations were detected in cases with synchronous USC and EIC. Strong p53 immunoreactivity was seen in the majority of USCs and EICs and correlated with p53 gene mutation, although lack of reactivity did not always indicate the absence of a gene mutation. Loss of heterozygosity of chromosome 17p was observed in 100% of USCs and in 43% of EICs, demonstrating that loss of the wild-type p53 allele occurs early in the development of serous carcinoma. Overall, our results reveal that p53 mutations are very common in USC and EIC. The presence of p53 gene mutations in EIC further suggests that p53 alteration plays an important role early in the pathogenesis of serous carcinoma, possibly accounting for its aggressive biological behavior.