Overexpression and mutation of p53 in endometrial carcinoma.
Overexpression and mutation of p53 in endometrial carcinoma.
复制标题
p53在子宫内膜癌中的过度表达和突变。
作者：
M. Kohler;A. Berchuck;A. Davidoff;P. Humphrey;R. Dodge;J. Iglehart;J. Soper;D. Clarke‐Pearson;R. Bast;J. Marks
应用单克隆抗体PAb 1801对107例速冻原发性子宫内膜腺癌和15例良性子宫内膜组织中p53蛋白进行免疫组化染色。在良性样本中未观察到染色，而在107例癌症中的22例（21%）中观察到与p53蛋白过度表达一致的癌细胞强烈核染色。p53过度表达在晚期胃癌中更常见，（III/IV期）癌症（41%）比早期（I/II期）癌症（9%）（P <0.001），也与非类胶质瘤组织学相关（P = 0.008）、腹膜细胞学阳性（P = 0.01）、子宫外转移（P = 0.003）和孕酮受体状态阴性（P = 0.04）。为了证实p53过度表达与突变之间的关系，我们用逆转录聚合酶链反应扩增了8例癌组织中p53 mRNA。DNA测序显示，在5种过表达p53的癌症中，每一种都存在点突变，而在3种没有过表达p53的癌症中发现了野生型序列。5个突变中的每一个都导致p53基因高度保守区域中的氨基酸取代，其中在其他癌症中发现了突变。进一步的研究是必要的，以确定是否p53过表达和晚期疾病之间的关联是由于肿瘤进展过程中的遗传病变的积累，或是否p53的改变赋予一个更致命的表型。
Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.
登录
查看更多内容
影响因子：
56.9
作者：
MALKIN, D;LI, FP;FRIEND, SH
通讯作者：
FRIEND, SH
人外周血淋巴细胞细胞周期中p53蛋白的表达。
影响因子：
3.7
作者：
Mercer,WE;Baserga,R
通讯作者：
Baserga,R
影响因子：
56.9
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
通讯作者：
HARRIS, CC
影响因子：
56.9
作者：
BAKER, SJ;MARKOWITZ, S;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1073/pnas.87.16.6166
发表时间：
1990-08-01
影响因子：
11.1
作者：
MERCER, WE;SHIELDS, MT;ULLRICH, SJ
通讯作者：
ULLRICH, SJ