Active TGF-β signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart

Verbeke, Sofie; Bertoni, Franco; Bacchini, Patrizia; Oosting, Jan; Sciot, Raf; Krenács, Tibor; Bovée, Judith V.M.G.

doi:10.1038/modpathol.2013.56

Cited by 24 publications

(18 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Four TMAs were assembled from formalin‐fixed, paraffin‐embedded tissue using standard procedures (Verbeke et al, ) using a 2‐mm diameter punch (3DHistech, Budapest, Hungary; three TMAs) or a 0.6‐mm diameter punch (Beecher Instruments, Silver Spring, MD; one TMA) as previously described (Verbeke et al, ) containing 42 angiosarcomas of bone and 19 angiosarcomas of soft tissue. Using a tape‐transfer system (Instrumedics, Hackensack, NJ, USA), 4‐μm sections were transferred to glass slides.…”

Section: Methodsmentioning

confidence: 99%

Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Verbeke

Jong

Bertoni

et al. 2014

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

Molecular genetic studies on vascular tumors are rare. Recently, possible involvement of MYC and KDR has been documented in a subset of angiosarcomas of soft tissue. We performed a cytogenetic analysis of primary angiosarcomas of bone (n = 13) and soft tissue (n = 5) using high density array-comparative genomic hybridization (array-CGH). Regions of interest were validated by fluorescence in situ hybridization (FISH). Antibodies for candidate genes (SKI, MYC, KDR, and MAPK9) were selected and immunohistochemistry was performed. Six angiosarcomas of bone and four angiosarcomas of soft tissue showed chromosomal losses, gains, and high level amplifications. Cluster analysis identified two groups: a group with a complex genetic profile and a group with only few genetic aberrations. Five regions of interest were selected, which were located at chromosome bands 1p36.23, 2q32-34, 5q35, 8q24, and 17q21.32-24.2. Interphase FISH confirmed the high-level amplifications. Immunohistochemical analysis showed high expression of MYC (16/60), MAPK9 (63/69), and SKI (52/62). There were no differences between the two groups with regards to location, immunohistochemical expression nor survival. In summary, we identified two subgroups of angiosarcoma: those with few or no gross aberrations and those which show numerous genetic aberrations consisting of chromosomal losses, gains and high level amplifications or complex aberrations. The most common finding was amplification of 2q and 17q in both angiosarcoma of bone and soft tissue, suggesting overlap in tumorigenesis irrespective of their location. We show MYC amplification in primary angiosarcoma indicating this is not entirely specific for radiation-induced angiosarcoma.

show abstract

Section: Methodsmentioning

confidence: 99%

Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Verbeke

Jong

Bertoni

et al. 2014

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…The importance of the PIK3CA/AKT pathways in angiosarcoma is evident based on the conserved association between abnormalities in this pathway and the appearance of HSA or angiosarcoma across dogs, humans, and zebrafish, three evolutionarily distant species. In humans, activation of PIK3 seems to occur through different mechanisms depending of the topography of the tumors, with deficiencies of PTEN seen more frequently in bone angiosarcomas and overexpression of KIT seen more frequently in soft tissue angiosarcomas [ 56 ]. However, a spontaneous mutation of the PTEN C2 domain resembling those seen in dogs also has been reported in a liver angiosarcoma from a human patient [ 57 ].…”

Section: Ontogeny Of Canine Hsamentioning

confidence: 99%

Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives

Kim

Graef

Dickerson

et al. 2015

Veterinary Sciences

View full text Add to dashboard Cite

Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous masses are often treatable by tumor excision, visceral tumors are almost always incurable. Treatment advances for this disease have been limited due to a poor understanding of the overall tumor biology. Based upon its histological appearance, HSA has been presumed to originate from transformed endothelial cells; however, accumulating data now suggest a pluripotent bone marrow progenitor as the cell of origin for this disease. More recently, the identification of a novel subclassification of HSAs has provided a foundation to further our understanding of the cellular characteristics of HSA tumor cells, along with those of the cells comprising the tumor microenvironment. These discoveries hold promise for the development of new approaches to improve treatments for canine HSA, as well as to establish the utility of this disease as a spontaneous model to understand the pathogenesis and develop new treatments for vascular tumors of humans. In this review, we will provide a brief historical perspective and pathobiology of canine HSA, along with a focus on the recent advances in the molecular and cellular understanding of these tumors. In addition, future directions that should continue to improve our understanding of HSA pathogenesis will be discussed.

show abstract

“…[23][24][25] In a large study of 91 angiosarcomas, 34% were positive for CD30. 23 CD117 reactivity, [26][27][28] in the proper clinical setting, could lead to a diagnosis of gastrointestinal stromal tumor. In all of these situations, In general, commonly used markers of melanocytic differentiation do not strongly label angiosarcoma.…”

Section: Resultsmentioning

confidence: 99%

“…In a large study of 91 angiosarcomas, 34% were positive for CD30 . CD117 reactivity, in the proper clinical setting, could lead to a diagnosis of gastrointestinal stromal tumor. In all of these situations, a panel of immunostains tailored to the particular histologic and clinical context is essential.…”

Section: Discussionmentioning

confidence: 99%

Index report of cutaneous angiosarcomas with strong positivity for tyrosinase mimicking melanoma with further evaluation of melanocytic markers in a large angiosarcoma series

et al. 2017

View full text Add to dashboard Cite

Cutaneous angiosarcoma can be challenging to diagnose particularly when poorly vasoformative and studied on biopsies. We report a case of a cutaneous angiosarcoma with strong positivity for tyrosinase, the first to our knowledge, initially misdiagnosed as melanoma. We subsequently evaluated the reactivity of panmelanocytic cocktail (tyrosinase, HMB-45 and Melan-A), SOX10, tyrosinase and MITF in a large tissue microarray (TMA) of angiosarcoma. The TMA included 142 cases of angiosarcomas (29 cutaneous, 22 primary breast, 41 post-radiation breast, 15 visceral, 26 deep soft tissue and bone, 5 chronic lymphedema-associated and 4 angiosarcomas arising in other sarcomas). Immunohistochemical studies were performed with anti-panmelanocytic cocktail, anti-SOX10, anti-MITF and anti-tyrosinase antibodies. TMA staining results were scored on intensity and percentage of tumoral labeling. Aside from the index case, no cases (0 of 133) showed positivity for tyrosinase including 28 cutaneous angiosarcomas. One breast angiosarcoma (1 of 131) was positive for MITF. All cases were negative for SOX10 and panmelanocytic cocktail (0 of 132). Angiosarcomas can rarely be positive for tyrosinase and MITF. Pathologists should be cognizant of these rare exceptions to prevent confusion with melanoma. Additional immunohistochemical markers for vascular and melanocytic differentiation, thorough histological examination for vasoformative and in situ areas as well as clinical impression are helpful in these exceptionally problematic cases.

show abstract

Active TGF-β signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart

Cited by 24 publications

References 57 publications

Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives

Index report of cutaneous angiosarcomas with strong positivity for tyrosinase mimicking melanoma with further evaluation of melanocytic markers in a large angiosarcoma series

Contact Info

Product

Resources

About