The Expanded Histologic Spectrum of Myxoid Liposarcoma With an Emphasis on Newly Described Patterns

Fritchie, Karen; Goldblum, John R.; Tubbs, Raymond R.; Sun, Yang; Carver, Paula; Billings, Steven D.; Rubin, Brian P.

doi:10.1309/ajcp90ynokbagcdm

Cited by 39 publications

(28 citation statements)

References 22 publications

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“…48 Our results support these observations, demonstrating that Dkk-1 alone can convert a relatively benign and well-differentiated OS cell line 17 into a more aggressive and primitive form. 49 Depending on the underlying tissue of origin, cancers with high levels of Dkk-1-expression have been reported both as being pro- and antimetastatic. 50 Although being more aggressive, none of the animals showed signs of metastasis when we examined the lungs.…”

Section: Discussionmentioning

confidence: 99%

An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity

et al. 2014

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It is widely accepted that canonical Wnt (cWnt) signaling is required for the differentiation of osteoprogenitors into osteoblasts. Furthermore, tumor-derived secretion of the cWnt-antagonist Dickkopf-1 (Dkk-1) is known to cause bone destruction, inhibition of repair and metastasis in many bone malignancies, but its role in osteosarcoma (OS) is still under debate. In this study, we examined the role of Dkk-1in OS by engineering its overexpression in the osteochondral sarcoma line MOS-J. Consistent with the known role of Dkk-1 in osteoblast differentiation, Dkk-1 inhibited osteogenesis by the MOSJ cells themselves and also in surrounding tissue when implanted in vivo. Surprisingly, Dkk-1 also had unexpected effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro and caused the formation of larger and more destructive tumors than controls upon orthotopic implantation. These effects were attributed in part to upregulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1). Direct inhibition of ALDH1 reduced viability under stressful culture conditions, whereas pharmacological inhibition of cWnt or overexpression of ALDH1 had a protective effect. Furthermore, we observed that ALDH1 was transcriptionally activated in a c-Jun-dependent manner through a pathway consisting of RhoA, MAP-kinase-kinase-4 and Jun N-terminal Kinase (JNK), indicating that noncanonical planar cell polarity-like Wnt signaling was the mechanism responsible. Together, our results therefore demonstrate that Dkk-1 enhances resistance of OS cells to stress by tipping the balance of Wnt signaling in favor of the non-canonical Jun-mediated Wnt pathways. In turn, this results in transcriptional activation of ALDH1 through Jun-responsive promoter elements. This is the first report linking Dkk-1 to tumor stress resistance, further supporting the targeting of Dkk-1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells.

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Section: Discussionmentioning

confidence: 99%

An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity

et al. 2014

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“…Myxoid liposarcoma can show a wide variation of histologic patterns, at times within the same tumor [12]. This can lead to difficult diagnoses, especially on small biopsy specimens.…”

Section: Discussionmentioning

confidence: 99%

Myxoid liposarcoma in a 91-year-old patient

Sheffield

Nielsen

2013

Mol Cytogenet

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BackgroundMyxoid liposarcoma is a mesenchymal malignancy most commonly presenting in young adults. This tumor is known for its characteristic chromosomal rearrangement at the DDIT3 locus.ResultsWe report a case of myxoid liposarcoma in a 91-year-old, the oldest known patient with this disease-entity. FISH analysis of the DDIT3 and FUS loci demonstrate the pathognomonic chromosomal alteration in the setting of predominantly round cell histology on biopsy, confirmed by RT-PCR.ConclusionMyxoid liposarcoma affects mostly young adults but can be seen in the elderly population. Molecular and cytogenetic assays are helpful auxiliaries to histology in the setting of unusual histology and clinical presentation.

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“…Various morphological patterns, e.g., traditional myxoid, traditional round cell, pulmonary edema-like, lipoblast-rich, island, lipomatous, stromal hyalinization, cord-like, nested ( Fig. 2 ), chondroid metaplasia, and hemangiopericytoma-like patterns, have been described [74] . The lack of specific IHC markers as well as the morphological heterogeneity underlines the use of FISH ( Fig.…”

Section: Myxoid Soft-tissue Tumorsmentioning

confidence: 99%

Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

2017

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Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor. In addition, novel molecular alterations detected by next-generation sequencing (NGS) obtain further insights into the pathogenesis of these rare tumors and allow a more detailed genetic classification. Based on our single-center results of NGS using the Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher Scientific) for mutational analyses as well as the Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) to detect gene fusions in 26 genes since early 2016, we have experienced NGS as a very sensitive method to detect genetic alterations. In our experience, the use of the Archer FusionPlex Sarcoma Kit is superior to fluorescent in situ hybridization as an auxiliary tool in the routine workup of soft-tissue and bone tumors.

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The Expanded Histologic Spectrum of Myxoid Liposarcoma With an Emphasis on Newly Described Patterns

Cited by 39 publications

References 22 publications

An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity

An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity

Myxoid liposarcoma in a 91-year-old patient

Role of Next-Generation Sequencing as a Diagnostic Tool for the Evaluation of Bone and Soft-Tissue Tumors

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