Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas
Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas
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DOI：
10.1007/s00428-005-0029-9
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发表时间：
2005-07
期刊：
影响因子：
3.5
通讯作者：
Yuzhen Feng;T. Shiozawa;A. Horiuchi;Hsien-Chang Shih;T. Miyamoto;H. Kashima;A. Suzuki;T. Nikaido;I. Konishi
中科院分区：
文献类型：
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作者：
Yuzhen Feng;T. Shiozawa;A. Horiuchi;Hsien-Chang Shih;T. Miyamoto;H. Kashima;A. Suzuki;T. Nikaido;I. Konishi
为了进一步阐明P53突变在子宫内膜癌中的意义，我们研究了P53在瘤内异质性表达的子宫内膜样癌中的表达。此外，我们还研究了P53突变与细胞周期蛋白A表达之间的相关性，因为我们先前报道了P53与细胞周期蛋白A之间的拓扑相关性。在54例P53阳性的子宫内膜癌中，23例(43%)有P53基因突变，且倾向于组织学分级较高的肿瘤。54例中有10例P53异质性表达，其中9例P53突变仅存在于P53阳性部位，常见于同一肿瘤Ki-67升高的组织学低分化区域。细胞周期蛋白A在P53阳性区域有表达，但在有P53突变的肿瘤(12/23，52%)和无P53突变的肿瘤(18/31，58%)中均有表达。这些结果表明，P53突变是一个晚期事件，在子宫内膜样腺癌恶性潜能的获得中起重要作用。出乎意料的是，P53蛋白本身的积累可能是细胞周期蛋白A过度表达的重要原因。
To further elucidate the significance of p53 mutation in endometrial carcinoma, we investigated it in endometrioid-type endometrial carcinomas showing intratumoral heterogeneous p53 expression. In addition, we also examined the correlation of p53 mutation and cyclin A expression, because we previously reported a topological correlation between the expression of p53 and cyclin A. The p53 mutation in exons 5–8 in 54 cases of endometrial carcinoma showing immunohistochemical expression of p53 was examined using microdissected tissue DNAs. Of the 54 p53-positive endometrial carcinomas, 23 (43%) had p53 mutation with a tendency in histologically higher grade tumors. Ten of the 54 showed a heterogeneous p53 expression, and in 9 of the 10 cases, p53 mutation was present only in p53-positive sites, which were often found in histologically less differentiated areas with elevated Ki-67 in the same tumor. Cyclin A expression was topologically observed in p53-positive areas; however, it was noted in both tumors with (12/23, 52%) and without (18/31, 58%) p53 mutation. These results suggest that p53 mutation is a late event and plays an important role in the acquisition of malignant potentials in endometrioid-type endometrial adenocarcinomas. Unexpectedly, accumulation of the p53 protein itself may be important in cyclin A overexpression.