title: Angiosarcoma: a tissue microarray study with diagnostic implications.
abstract: BACKGROUND
  Angiosarcoma (AS) is a rare soft tissue sarcoma showing endothelial differentiation as indicated by morphology and expression of CD31 (blood), D2-40 (lymphatic), factor VIII, and CD34 (both). We sought to examine the pattern of immunohistochemical markers of differentiation in AS and correlate these with outcome.
  
  
  METHODS
  An AS tissue microarray (n = 70 specimens) was constructed for immunohistochemical analysis of CD31, CD34, factor VIII, D2-40, and pan-cytokeratin. Samples on this array were linked to clinicopathologic and outcome data for these patients. Univariate analyses were used to explore disease-specific survival (DSS) factors.
  
  
  RESULTS
  Nine metastatic, 23 localized, and 4 recurrent cases were included. Information about the tissue status (ie, primary or metastasis) was unavailable in 4 patients. Primary sites for the tumor included bone (n = 1), breast parenchyma (n = 11), breast skin (n = 4), heart (n = 5), skin (n = 8), soft tissue (n = 7), and unknown (n = 3). Three patients presented with multifocal disease (primary sites in these patients included breast, skin, and soft tissue). Metastatic sites included lung, bone, lymph nodes, brain, liver, and parotid. Of the 40 cases, 8 (20%) showed a pure or predominant epithelioid histology. Of the biomarkers evaluated by tissue microarray, 92% of tumors expressed at least one endothelial marker (factor VIII = 83%, CD31 = 80%, CD34 = 63%, and D2-40 = 43%) with 88% expressing 2 or more markers. Eighty-eight percent of tumors expressing D2-40 coexpressed CD31, an unusual combination in normal vessels. No endothelial marker clearly associated with disease-specific survival. Fifty percent (4/8) of epithelioid cases and 9% (3/32) of nonepithelioid cases showed keratin expression.
  
  
  CONCLUSIONS
  Unusual patterns and loss of endothelial markers are common in AS, suggesting use of multiple markers in challenging cases and perhaps indicating important biologic characteristics.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. prao@mdanderson.org
authors.forename: Priya
authors.initials: P
authors.lastname: Rao
authors.forename: Guy
authors.initials: G
authors.lastname: Lahat
authors.forename: Christina
authors.initials: C
authors.lastname: Arnold
authors.forename: Alde Carlo
authors.initials: AC
authors.lastname: Gavino
authors.forename: Sharon
authors.initials: S
authors.lastname: Lahat
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000737:chemistry* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006394:Hemangiosarcoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011237:Predictive Value of Tests; D012983:Soft Tissue Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C500987:monoclonal antibody D2-40; D007633:Keratins; C078147:F8 protein, human; D005169:Factor VIII