Molecular Variability of TLS - CHOP Structure Shows No Significant Impact on the Level of Adipogenesis: A Comparative Ultrastructural and RT-PCR Analysis of 14 Cases of Myxoid/Round Cell Liposarcomas

Abstract

A specific TLS-CHOP fusion gene derived from the t(12;16) is present in at least 95% of myxoid/round cell liposarcomas (MLS). Rare cases of MLS show a variant t(12;22) translocation, resulting in EWS-CHOP fusion gene. The CHOP gene encodes a leucine-zipper transcription factor, which is implicated in both oncogenic transformation and inhibition of adipogenesis. To examine whether the molecular variability of TLS-CHOP or EWS-CHOP fusion transcript structure is associated with the degree of inhibition of adipogenesis, a comparative ultrastructural and RT-PCR-based analysis of 14 MLS was performed. The specimens consisted of 9 primary, 2 locally recurrent tumors, and one representative sample each from 3 patients with multifocal soft tissue metastases. Histologically, there were 8 high-grade and 6 low-grade MLS using 5% round cell (RC) component as the cutoff point. By RT-PCR assay there were 13 cases with TLS-CHOP fusion transcripts: 7 cases of type 5-2 (known as type II), 4 cases of type 7-2 (known as type I),1 case of type 8-2 (known as type III), and 1 unique case of type 6-2.The remaining 1 case showed an EWS-CHOP fusion transcript. Ultrastructural examination revealed that tumor cells were composed of a moderate-to-predominant proportion of well-formed lipoblasts in 4 cases, while in 6 cases such lipoblasts were very scant.The remaining 4 tumors were arrested in the stage of transitional cells. The heterogeneity of TLS-CHOP fusion transcript showed no apparent impact on adipogenesis, since both TLS-CHOP type I and II cases could randomly display various levels of lipoblastic differentiation. Furthermore, the 4 cases without definite lipoblasts showed no preference for any specific fusion variants and consisted of one each of TLS-CHOP subtypes. In addition, the fusion transcript variants did not correlate with other ultrastructural features, such as the presence and amount of glycogen, mitochondria, rough endoplasmic reticulum, vimentin-like intermediate filaments, and external lamina. However, there appeared to have a trend suggesting the predilections of glycogen particles and vimentin-like intermediate filaments in primitive mesenchymal cells and/or transitional cells. These findings cannot substantiate the hypothesis that the molecular variability of fusion transcripts has a biological impact on adipogenesis of MLS, and other factors might be implicated in their level of differentiation.