Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases with Morphologic Reappraisal
Identifieur interne : 007564 ( Ncbi/Curation ); précédent : 007563; suivant : 007565Frequent FOS Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases with Morphologic Reappraisal
Auteurs : Shih-Chiang Huang [Taïwan, États-Unis] ; Lei Zhang [États-Unis] ; Yun-Shao Sung [États-Unis] ; Chun-Liang Chen [États-Unis] ; Thomas Krausz [États-Unis] ; Brendan C. Dickson [Canada] ; Yu-Chien Kao [Taïwan] ; Narasimhan P. Agaram [États-Unis] ; Christopher D. M. Fletcher [États-Unis] ; Cristina R. Antonescu [États-Unis]Source :
- The American journal of surgical pathology [ 0147-5185 ] ; 2015.
Abstract
Epithelioid hemangioma (EH) is a unique benign vasoformative tumor composed of epithelioid endothelial cells. Although a small subset of EHs with atypical features harbor
Url:
DOI: 10.1097/PAS.0000000000000469
PubMed: 26135557
PubMed Central: 4567921
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Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases with Morphologic Reappraisal</title>
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Gene Rearrangements in Epithelioid Hemangioma: A Molecular Study of 58 Cases with Morphologic Reappraisal</title>
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<author><name sortKey="Sung, Yun Shao" sort="Sung, Yun Shao" uniqKey="Sung Y" first="Yun-Shao" last="Sung">Yun-Shao Sung</name>
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<author><name sortKey="Chen, Chun Liang" sort="Chen, Chun Liang" uniqKey="Chen C" first="Chun-Liang" last="Chen">Chun-Liang Chen</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
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<country xml:lang="fr">États-Unis</country>
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</placeName>
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</affiliation>
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<author><name sortKey="Kao, Yu Chien" sort="Kao, Yu Chien" uniqKey="Kao Y" first="Yu-Chien" last="Kao">Yu-Chien Kao</name>
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<country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City</wicri:regionArea>
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<author><name sortKey="Agaram, Narasimhan P" sort="Agaram, Narasimhan P" uniqKey="Agaram N" first="Narasimhan P" last="Agaram">Narasimhan P. Agaram</name>
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<placeName><region type="state">État de New York</region>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Pathology, Brigham and Women's Hospital, Boston</wicri:cityArea>
</affiliation>
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<author><name sortKey="Antonescu, Cristina R" sort="Antonescu, Cristina R" uniqKey="Antonescu C" first="Cristina R." last="Antonescu">Cristina R. Antonescu</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
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<front><div type="abstract" xml:lang="en"><p id="P1">Epithelioid hemangioma (EH) is a unique benign vasoformative tumor composed of epithelioid endothelial cells. Although a small subset of EHs with atypical features harbor <italic>ZFP36-FOSB</italic>
fusions, no additional genetic abnormalities have been found to date in the remaining cases. Based on a novel <italic>FOS-LMNA</italic>
gene fusion identified by RNA sequencing in an index case of a skeletal EH with typical morphology, we sought to investigate the prevalence of <italic>FOS</italic>
rearrangement in a large cohort of EHs. Thus 57 additional EH cases lacking <italic>FOSB</italic>
rearrangements were studied for <italic>FOS</italic>
gene abnormalities by FISH and results were correlated with morphologic appearance and clinical presentation. The EHs were subclassified as typical (n=25), cellular (n=21) and ALHE (angiolymphoid hyperplasia with eosinophilia)(n=12) variants. The ALHE was defined as an EH with a vascular ‘blow-out’ pattern associated with a variable degree of inflammation. There were 17 (29%) cases bearing <italic>FOS</italic>
gene rearrangements among 58 cases tested, including 12 males and 5 females, with a mean age of 42 years. Most <italic>FOS</italic>
-rearranged EHs occurred in the bone (10) and soft tissue (6), while only one case was cutaneous. The predominant anatomic site was the extremity (12), followed by trunk (3), head and neck (1), and penis (1). The incidence of <italic>FOS</italic>
rearrangement was significantly higher in bone (59%, p = 0.006) and lower in head and neck (5%, p = 0.009). Twelve of the <italic>FOS</italic>
rearranged cases were cellular EH (p = 0.001) associated with moderate mitotic activity (2-5/10 HPF) and milder inflammatory background. All 12 ALHE cases lacked <italic>FOS</italic>
gene abnormalities, suggesting different pathogenesis. In conclusion, <italic>FOS</italic>
rearrangement was present in a third of EHs across different locations and histologic variants; however, it was more prevalent in cellular EH and intra-osseous lesions, compared to those in skin, soft tissue and head and neck. This genetic abnormality can be useful in challenging cases, to distinguish cellular EHs from malignant epithelioid vascular tumors. These results also suggest that dysregulation of the FOS family of transcription factors through chromosomal translocation is as a key event in the tumorigenesis of EH except for the ALHE variant.</p>
</div>
</front>
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