title: Expression of FKBP12 in benign and malignant vascular endothelium: an immunohistochemical study on conventional sections and tissue microarrays.
abstract: FKBP12 is a cytosolic FK506 binding protein that interacts with calcineurin and thereby mediates the immunosuppressive effects of FK506. Because initial immunohistochemical staining showed abundant expression of FKBP12 in vascular endothelial cells, we evaluated whether it could serve as a marker for vascular neoplasms. We performed immunohistochemical staining of conventional sections from formalin-fixed, paraffin-embedded tissue from 59 benign and malignant vascular neoplasms using a polyclonal rabbit antiserum against FKBP12. Western blot analysis of tissue from 6 angiosarcomas showed a single band at 12 kD, consistent with the published molecular weight for the FKBP12 protein. Together, CD31, CD34, and FKBP12 identified all 59 vascular neoplasms in this study. Specificity of immunohistochemical staining was assessed on 1,321 tissues represented on 7 tissue microarrays. All proteins were occasionally expressed in non-vascular tissue. Six of 8 vascular neoplasms represented on the arrays stained for FKBP12, as did normal vessels in numerous cores. The polyclonal antiserum shows comparable sensitivity (94.9%) and specificity (96.5%) to CD34 and CD31 and may be a useful additional marker for vascular differentiation. Because we have evaluated a large number of tissues by tissue microarray, we anticipate that our estimate of the specificity of immunostaining for FKBP12 as a marker for vascular endothelium will be accurate. In addition, our findings may explain the toxic effects of FK506 on vascular endothelium of the kidney.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, California, USA. john.higgins@Stanford.EDU
authors.forename: John P T
authors.initials: JP
authors.lastname: Higgins
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Lingli
authors.initials: L
authors.lastname: Wang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Domanay
authors.forename: Roger A
authors.initials: RA
authors.lastname: Warnke
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D018323:Hemangioendothelioma, Epithelioid / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006391:Hemangioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006394:Hemangiosarcoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016591:Histocytological Preparation Techniques; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism; D009383:Neoplasms, Vascular Tissue / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D022061:Tacrolimus Binding Protein 1A / Q000032:analysis / Q000096:biosynthesis*; D019043:Vascular Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D022061:Tacrolimus Binding Protein 1A