title: Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy.
abstract: BACKGROUND
  Tumors of endothelium range from benign hemangiomas of infancy to highly malignant angiosarcomas of the elderly. Hemangiomas are the most common tumors in infants and may affect up to 10% of all children. The biologic behavior of these lesions ranges from self-resolving, in the case of hemangiomas and pyogenic granulomas, to lethal metastatic neoplasms in the case of angiosarcoma. Although the clinical outcomes of these diseases are easily distinguished, the biologic basis for these differences is not well understood. Activation of mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that may predict response of a tumor to chemotherapy.
  
  
  OBJECTIVE
  Our purpose was to examine expression of phosphorylated (activated) MAPK in hemangiomas of infancy, pyogenic granulomas, hemangioendotheliomas, and angiosarcomas to determine whether phosphorylated MAPK was expressed in endothelial tumors. In addition, we examined endothelial tumors of infectious origin, Kaposi's sarcoma, and verruga peruana.
  
  
  METHODS
  Skin sections from benign and malignant endothelial tumors, including hemangioma of infancy, angiosarcoma, and infectious endothelial lesions (Kaposi's sarcoma, verruga peruana) were stained with an antibody specific for phosphorylated MAPK.
  
  
  RESULTS
  We demonstrated strong expression of phosphorylated MAPK in benign endothelial tumors, including capillary hemangioma of infancy and pyogenic granuloma, and greatly decreased expression in angiosarcoma. In addition, infectious endothelial tumors stained strongly with this antibody, similar to benign tumors. The presence of immunoreactive phosphorylated MAPK appears to be inversely correlated with degree of malignancy.
  
  
  CONCLUSIONS
  We demonstrate that the use of antibodies specific for signal transduction pathways is feasible in paraffin-fixed tissue. Thus the activity of a given signal transduction pathway can be ascertained in a biopsy specimen. Immunohistochemistry for phosphorylated MAPK may help the pathologist distinguish benign from malignant endothelial processes and thus guide therapy.
authors.affiliation: Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA. jarbise@emory.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: S W
authors.initials: SW
authors.lastname: Weiss
authors.forename: Z K
authors.initials: ZK
authors.lastname: Arbiser
authors.forename: F
authors.initials: F
authors.lastname: Bravo
authors.forename: B
authors.initials: B
authors.lastname: Govindajaran
authors.forename: H
authors.initials: H
authors.lastname: Caceres-Rios
authors.forename: G
authors.initials: G
authors.lastname: Cotsonis
authors.forename: S
authors.initials: S
authors.lastname: Recavarren
authors.forename: R A
authors.initials: RA
authors.lastname: Swerlick
authors.forename: C
authors.initials: C
authors.lastname: Cohen
mesh_terms: D017789:Granuloma, Pyogenic / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006390:Hemangioendothelioma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006391:Hemangioma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D009383:Neoplasms, Vascular Tissue / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D014860:Warts / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology
chemical_list: D020928:Mitogen-Activated Protein Kinases