జర్నల్ ఆఫ్ క్లినికల్ & ఎక్స్‌పెరిమెంటల్ పాథాలజీ

నైరూప్య

Immunohistochemical and Fluorescence In Situ Hybridization Analysis of Angiosarcoma of Soft Tissue and Bone Including those Occurring in Unusual Backgrounds

Bibianna Purgina, Michael Nalesnik, Kathleen Cieply, Kimberly Fuhrer, Mark Goodman, Richard McGough and Uma N.M. Rao

Background: Angiosarcomas (AS) are high-grade sarcomas that comprise less than 1% of soft tissue sarcomas. We compared clinical, pathological and molecular features of primary and recurrent conventional AS, including cases occurring in unusual backgrounds, such as organ transplants, at a site of metal orthopedic implant, and at a site of prior trauma.
Materials and Methods: Paraffin blocks from 15 patients with AS were retrieved from our archives. Ten patients had recurrent AS, 4 patients had metastases. AS were morphologically categorized them into epithelioid and conventional types. Immunohistochemical stains included three vascular markers, cytokeratins, Akt, Ki67, HHV8 and EBV in paired samples of primary and recurrent/metastatic AS. Fluorescence In Situ Hybridization (FISH) analysis for Epidermal Growth Factor Receptor (EGFR) and Hepatocyte Growth Factor Receptor (MET) was performed on all AS samples.
Results: Conventional AS were positive for more than two vascular markers and negative for cytokeratins. Epithelioid AS demonstrated variable positivity for vascular markers and cytokeratins. All tumors were negative for HHV8 and EBV. All AS displayed cytoplasmic immunopositivity for the phosphorylated forms of Akt.
Conclusion: AS with epithelioid features had fewer positive vascular markers, possibly reflecting a lack of differentiation. There were no differences in pattern of immunoreactivity between post-transplant and conventional AS and primary and metastatic AS. No amplification of either EGFR or MET was found but a majority of the cases demonstrated hyperploidy and three cases demonstrated monosomy for EGFR in greater than 50% of cells. Both MET and EGFR are located on chromosome 7 and the detected hyperploidy and monosomy of these two genes are likely related to copy number alterations of chromosome 7. It is unlikely that these two genes play a role in biology of AS. AS with epithelioid features and metal associated AS, which are extremely rare, had an aggressive clinical course.