Mutation of TP53 gene is involved in carcinogenesis of hepatic undifferentiated (embryonal) sarcoma of the adult, in contrast with Wnt or telomerase pathways:: an immunohistochemical study of three cases with genomic relation in two cases
Mutation of TP53 gene is involved in carcinogenesis of hepatic undifferentiated (embryonal) sarcoma of the adult, in contrast with Wnt or telomerase pathways:: an immunohistochemical study of three cases with genomic relation in two cases
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DOI：
10.1016/j.jhep.2004.10.021
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发表时间：
2005-03-01
影响因子：
25.7
通讯作者：
Bioulac-Sage, P
中科院分区：
文献类型：
--
作者：
Lepreux, S;Rebouissou, S;Bioulac-Sage, P
背景/目的：肝未分化（胚胎）肉瘤（HUS）是一种罕见的成人肝脏恶性肿瘤。方法：本研究对3例成人HUS的3种经典致癌途径即TP 53（p53）、Wnt（CTNNB 1/beta-catenin和AXIN 1）和端粒酶（hTERT）通路进行了研究。结果：免疫组化显示80%以上的肿瘤细胞p53过表达，其中2例为TP 53基因突变，1例为全基因组等位基因AXIN 1和CTNNB 1/beta-catenin基因突变。此外，在两个病例中观察到TP 53的突变，涉及序列特异性DNA结合结构域。CTNNB 1/beta-catenin和AXIN 1基因未发现突变。肿瘤细胞未显示hTERT染色，也未显示β-连环蛋白的核表达。1例HUS患者染色体7 p、11 p、17 p、22 q杂合性缺失，1 p、8 p、20 q等位基因不平衡。结论：在3例HUS患者中，我们强调TP 53通路在这种罕见肿瘤的发生中的作用。这一点可能是治疗策略的兴趣所在。(c)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exceptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases.Methods: In this study concerning three cases of HUS occurring in adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p53), Wnt (CTNNB1/beta-catenin and AXIN1) and telomerase (hTERT) pathways. We studied the expression of p53, beta-catenin and telomerase catalytic subunit hTERT by immunohistochemistry in the three cases; we determined TP53 gene mutation in two cases and the genome-wide allelotype, AXIN1, and CTNNB1/beta-catenin gene mutation in one case.Results: Immunohistochemistry showed an overexpression of p53 in more than 80 % of tumoral cells; furthermore, mutations of TP53 were observed in two cases, involving the sequence-specific DNA binding domain. In contrast, no mutation was found in CTNNB1/beta-catenin and AXIN1 genes. Tumoral cells did not show hTERT staining nor nuclear expression of beta-catenin. In addition, allelotype analysis in one case showed loss of heterozygosity of chromosome 7p, 11p, 17p, 22q, and allelic imbalance of 1p, 8p, 20q.Conclusions: In this report of HUS in three adult patients, we emphasize the role of TP53 pathway in carcinogenesis of this rare tumor. This point could be of interest for therapeutic strategies. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.