6615

SNAI1

SLUGH2|SNA|SNAH|SNAIL|SNAIL1|dJ710H13.1;snail homolog 1 (Drosophila);SNAI1;snail homolog 1 (Drosophila)

protein sna|protein snail homolog 1|snail 1 homolog|snail 1 zinc finger protein|snail 1, zinc finger protein|zinc finger protein SNAI1

20q13.2

protein-coding

Nested stromal epithelial tumor of the liver is a rare neoplasm of early childhood and adolescence with a characteristic nested morphology of spindle andepithelioid cells. Histogenesis and pathogenesis of this neoplasm are, however, still unclear. Because the characteristic nested morphology with spindle mesenchymal and epithelioid cells is suggestive of altered mesenchymal-epithelial transition and beta-catenin mutations are rather common in other liver tumors such as hepatoblastomas, we investigated the beta-catenin gene in 2 nested stromal epithelial tumors of the liver and analyzed additional factors involved in mesenchymal-epithelial transition, such as E-cadherin, vimentin, c-Met, TWIST, SNAIL, and SLUG by molecular genetic and immunohistochemical methods. mutation analysis of both cases revealed large deletions in exon 3 of the beta-catenin gene (155 and 228 base pairs), resulting in an accumulation of beta-catenin in the cytoplasm and nuclei of tumor cells, as evidenced by immunohistochemistry. The expression of the mesenchymal-epithelial transition factors SNAIL, SLUG, TWIST, c-Met, vimentin, and beta-catenin was generally increased, whereas E-cadherin was decreased. Morphological and immunohistochemical analysis, however, showed a variable expression pattern of various epithelial and mesenchymal markers both in the spindle and epithelioid cell compartments of thetumors, thus illustrating the transitional status of the tumor cells. In conclusion, our data clearly identify protein stabilizing mutations of the beta-catenin gene as a common feature of nested stromal epithelial tumors of theliver, similarly as in hepatoblastomas. Therefore, nested stromal epithelial tumors of the liver may be regarded as a variant of hepatoblastoma, despite differing from it in clinical and morphological aspects. The characteristic epithelioid-spindle morphology along with the incomplete epithelial differentiation proposes impaired mesenchymal-epithelial transition as a possible pathogenetic mechanism of this rare tumor. However, because only 2 cases were studied, this hypothesis awaits further validation.#CI- Copyright (c) 2012 Elsevier Inc. ALL rights reserved.