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 Journal Article


Authors: Huang, H. Y.; Antonescu, C. R.
Article Title: 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-CHOPtype 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.
Keywords: adolescent; adult; clinical article; controlled study; human tissue; aged; middle aged; human cell; histopathology; antineoplastic agent; cancer grading; microscopy, electron; reverse transcription polymerase chain reaction; cell maturation; molecular dynamics; genetic variability; cell differentiation; cell type; tissue section; correlation analysis; hybrid protein; reverse transcriptase polymerase chain reaction; rna, messenger; tumor recurrence; tumor cell; fusion gene; oncogene proteins, fusion; intermethod comparison; rna, neoplasm; mitochondrion; lipogenesis; mesenchyme; soft tissue neoplasms; transitional cell; ccaat-enhancer-binding proteins; myxosarcoma; rt-pcr; vimentin; rna-binding protein ews; soft tissue metastasis; rna-binding protein fus; adipogenesis; adipocytes; cell ultrastructure; glycogen; tls-chop; liposarcoma, myxoid; transcription factor chop; rough endoplasmic reticulum; humans; human; male; female; priority journal; article; ews-chop; ews chop fusion gene; lipoblast; round cell; tls chop fusion gene
Journal Title: Ultrastructural Pathology
Volume: 27
Issue: 4
ISSN: 0191-3123
Publisher: Informa Healthcare  
Date Published: 2003-01-01
Start Page: 217
End Page: 226
Language: English
DOI: 10.1080/01913120309917
PUBMED: 12907366
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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  1. Hsuan-Yin Huang
    23 Huang
  2. Cristina R Antonescu
    895 Antonescu