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TP53突变分析支持膀胱双相性肉瘤样尿路上皮癌(癌肉瘤)的单克隆起源。

TP53 mutational analysis supports monoclonal origin of biphasic sarcomatoid urothelial carcinoma (carcinosarcoma) of the urinary bladder.

作者信息

Armstrong Andrew B, Wang Mingsheng, Eble John N, MacLennan Gregory T, Montironi Rodolfo, Tan Puay-Hoon, Lopez-Beltran Antonio, Zhang Shaobo, Baldridge Lee Ann, Spartz Helena, Cheng Liang

机构信息

Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

出版信息

Mod Pathol. 2009 Jan;22(1):113-8. doi: 10.1038/modpathol.2008.176. Epub 2008 Nov 7.

DOI:10.1038/modpathol.2008.176
PMID:18997737
Abstract

Sarcomatoid urothelial carcinoma of the urinary bladder is an uncommon neoplasm with biphasic morphology exhibiting both epithelial and sarcomatoid components. Whether this tumor arises from a single cancer stem cell with subsequent differentiation or represents collision of the progeny of two separate cancer stem cells is a matter of controversy. To clarify its clonal origin, we analyzed the TP53 mutation status of a series of 17 sarcomatoid urothelial carcinomas using single-strand conformation polymorphism, DNA sequencing and p53 immunohistochemistry. Sarcomatoid and epithelial tumor components were separately microdissected using laser capture microdissection. Five out of the 17 sarcomatoid urothelial carcinomas contained TP53 point mutations in exons 5 and 8. In all five cases, the TP53 point mutations were identical in both the epithelial and sarcomatoid components. The sarcomatoid and epithelial tumor components in all 17 cases showed concordant p53 expression patterns. Our results suggest that despite their conspicuous divergence at the phenotypic level, the sarcomatoid and carcinomatoid elements of this uncommon tumor share a common clonal origin.

摘要

膀胱肉瘤样尿路上皮癌是一种罕见的肿瘤,具有双相形态,表现出上皮和肉瘤样成分。这种肿瘤是起源于单个癌症干细胞随后分化,还是代表两个独立癌症干细胞后代的碰撞,这是一个有争议的问题。为了阐明其克隆起源,我们使用单链构象多态性、DNA测序和p53免疫组织化学分析了一系列17例膀胱肉瘤样尿路上皮癌的TP53突变状态。使用激光捕获显微切割分别对肉瘤样和上皮肿瘤成分进行显微切割。17例膀胱肉瘤样尿路上皮癌中有5例在第5和第8外显子中存在TP53点突变。在所有5例中,上皮和肉瘤样成分中的TP53点突变是相同的。所有17例中的肉瘤样和上皮肿瘤成分均显示出一致的p53表达模式。我们的结果表明,尽管这种罕见肿瘤的肉瘤样和癌样成分在表型水平上有明显差异,但它们具有共同的克隆起源。

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