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

Background/Aims: Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exc eptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases. Methods: In this study concerning three cases of HUS occurring i n adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p5 3), Wnt (CTNNB1/β - catenin and AXIN1) and telomerase (hTERT) pathways. We stu died the expression of p53, β - 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/β - catenin gen e mutation in one case. Results: Immunohistochemistry showed an overexpression o f p53 in more than 80% of tumoral cells; furthermore, mutations of TP53 were o bserved in two cases, involving the sequence- specific DNA binding domain. In c ontrast, no mutation was found in CTNNB1/β - catenin and AXIN1 genes. Tumoral cells did not show hTERT staining nor nuclear expression of β - catenin. In ad dition, allelotype analysis in one case showed loss of heterozygosity of chromos ome 7p, 11p, 17p, 22q, and allelic imbalance of 1p, 8p, 20q. Conclusions: In thi s report of HUS in three adult patients, we emphasize the role of TP53 pathway i n carcinogenesis of this rare tumor. This point could be of interest for therape utic strategies.