Expression of FKBP12 in benign and malignant vascular endothelium: An immunohistochemical study on conventional sections and tissue microarrays
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 fo...
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creator | HIGGINS, John P. T MONTGOMERY, Kelli LINGLI WANG DOMANAY, Elizabeth WARNKE, Roger A BROOKS, James D VAN DE RIJN, Matt |
description | 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. |
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T ; MONTGOMERY, Kelli ; LINGLI WANG ; DOMANAY, Elizabeth ; WARNKE, Roger A ; BROOKS, James D ; VAN DE RIJN, Matt</creator><creatorcontrib>HIGGINS, John P. T ; MONTGOMERY, Kelli ; LINGLI WANG ; DOMANAY, Elizabeth ; WARNKE, Roger A ; BROOKS, James D ; VAN DE RIJN, Matt</creatorcontrib><description>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.</description><identifier>ISSN: 0147-5185</identifier><identifier>EISSN: 1532-0979</identifier><identifier>DOI: 10.1097/00000478-200301000-00007</identifier><identifier>PMID: 12502928</identifier><identifier>CODEN: AJSPDX</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Blotting, Western ; Dermatology ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; Hemangioendothelioma, Epithelioid - blood supply ; Hemangioendothelioma, Epithelioid - metabolism ; Hemangioendothelioma, Epithelioid - pathology ; Hemangioma - blood supply ; Hemangioma - metabolism ; Hemangioma - pathology ; Hemangiosarcoma - blood supply ; Hemangiosarcoma - metabolism ; Hemangiosarcoma - pathology ; Histocytological Preparation Techniques ; Humans ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Medical sciences ; Miscellaneous. Technology ; Neoplasm Proteins - metabolism ; Neoplasms, Vascular Tissue - blood supply ; Neoplasms, Vascular Tissue - metabolism ; Neoplasms, Vascular Tissue - pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Rabbits ; Sarcoma, Kaposi - blood supply ; Sarcoma, Kaposi - metabolism ; Sarcoma, Kaposi - pathology ; Sensitivity and Specificity ; Tacrolimus Binding Protein 1A - analysis ; Tacrolimus Binding Protein 1A - biosynthesis ; Tumors of the skin and soft tissue. 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T</creatorcontrib><creatorcontrib>MONTGOMERY, Kelli</creatorcontrib><creatorcontrib>LINGLI WANG</creatorcontrib><creatorcontrib>DOMANAY, Elizabeth</creatorcontrib><creatorcontrib>WARNKE, Roger A</creatorcontrib><creatorcontrib>BROOKS, James D</creatorcontrib><creatorcontrib>VAN DE RIJN, Matt</creatorcontrib><title>Expression of FKBP12 in benign and malignant vascular endothelium: An immunohistochemical study on conventional sections and tissue microarrays</title><title>The American journal of surgical pathology</title><addtitle>Am J Surg Pathol</addtitle><description>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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Western</subject><subject>Dermatology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>Hemangioendothelioma, Epithelioid - blood supply</subject><subject>Hemangioendothelioma, Epithelioid - metabolism</subject><subject>Hemangioendothelioma, Epithelioid - pathology</subject><subject>Hemangioma - blood supply</subject><subject>Hemangioma - metabolism</subject><subject>Hemangioma - pathology</subject><subject>Hemangiosarcoma - blood supply</subject><subject>Hemangiosarcoma - metabolism</subject><subject>Hemangiosarcoma - pathology</subject><subject>Histocytological Preparation Techniques</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Medical sciences</subject><subject>Miscellaneous. Technology</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasms, Vascular Tissue - blood supply</subject><subject>Neoplasms, Vascular Tissue - metabolism</subject><subject>Neoplasms, Vascular Tissue - pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Rabbits</subject><subject>Sarcoma, Kaposi - blood supply</subject><subject>Sarcoma, Kaposi - metabolism</subject><subject>Sarcoma, Kaposi - pathology</subject><subject>Sensitivity and Specificity</subject><subject>Tacrolimus Binding Protein 1A - analysis</subject><subject>Tacrolimus Binding Protein 1A - biosynthesis</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><subject>Vascular Neoplasms - blood supply</subject><subject>Vascular Neoplasms - metabolism</subject><subject>Vascular Neoplasms - pathology</subject><issn>0147-5185</issn><issn>1532-0979</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1OxCAUhYnR6PjzCoaNyypc6BTcqRl_ookudN1QeutgWjqB1jhP4StLdVQ23HvynXOTQwjl7JQzXZyx6clCZcCYYDwt2aQUW2TGcwFZYvQ2mTEuiyznKt8j-zG-McZBcdglexxyBhrUjHwuPlYBY3S9p31Dr-8vnzhQ52mF3r16anxNO9Om0fiBvptox9YEir7uhyW2buzO6YWnrutG3y9dHHq7xM5Z09I4jPWaplzb-3f0QzoxqWinKX4nDy7GEWniQ29CMOt4SHYa00Y82vwH5OV68Xx1mz083txdXTxkFtR8yBRHXbHc1hKhmVcIqkIJAqQUGgqrJTKO1gqlRa6ruWiKvNBcgzCVTjSIA6J-ctPlGAM25Sq4zoR1yVk5dVz-dlz-dfwtFcl6_GNdjVWH9b9xU2oCTjZAqsu0TTDeuvjPSZlzEFp8AXhPhqQ</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>HIGGINS, John P. 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T ; MONTGOMERY, Kelli ; LINGLI WANG ; DOMANAY, Elizabeth ; WARNKE, Roger A ; BROOKS, James D ; VAN DE RIJN, Matt</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c286t-81e9b05cd4e2f6be28be4232443927c94e01ecc389359b63f75791923ab9be223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Western</topic><topic>Dermatology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - pathology</topic><topic>Hemangioendothelioma, Epithelioid - blood supply</topic><topic>Hemangioendothelioma, Epithelioid - metabolism</topic><topic>Hemangioendothelioma, Epithelioid - pathology</topic><topic>Hemangioma - blood supply</topic><topic>Hemangioma - metabolism</topic><topic>Hemangioma - pathology</topic><topic>Hemangiosarcoma - blood supply</topic><topic>Hemangiosarcoma - metabolism</topic><topic>Hemangiosarcoma - pathology</topic><topic>Histocytological Preparation Techniques</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Medical sciences</topic><topic>Miscellaneous. Technology</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasms, Vascular Tissue - blood supply</topic><topic>Neoplasms, Vascular Tissue - metabolism</topic><topic>Neoplasms, Vascular Tissue - pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Rabbits</topic><topic>Sarcoma, Kaposi - blood supply</topic><topic>Sarcoma, Kaposi - metabolism</topic><topic>Sarcoma, Kaposi - pathology</topic><topic>Sensitivity and Specificity</topic><topic>Tacrolimus Binding Protein 1A - analysis</topic><topic>Tacrolimus Binding Protein 1A - biosynthesis</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><topic>Vascular Neoplasms - blood supply</topic><topic>Vascular Neoplasms - metabolism</topic><topic>Vascular Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HIGGINS, John P. T</creatorcontrib><creatorcontrib>MONTGOMERY, Kelli</creatorcontrib><creatorcontrib>LINGLI WANG</creatorcontrib><creatorcontrib>DOMANAY, Elizabeth</creatorcontrib><creatorcontrib>WARNKE, Roger A</creatorcontrib><creatorcontrib>BROOKS, James D</creatorcontrib><creatorcontrib>VAN DE RIJN, Matt</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The American journal of surgical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HIGGINS, John P. T</au><au>MONTGOMERY, Kelli</au><au>LINGLI WANG</au><au>DOMANAY, Elizabeth</au><au>WARNKE, Roger A</au><au>BROOKS, James D</au><au>VAN DE RIJN, Matt</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of FKBP12 in benign and malignant vascular endothelium: An immunohistochemical study on conventional sections and tissue microarrays</atitle><jtitle>The American journal of surgical pathology</jtitle><addtitle>Am J Surg Pathol</addtitle><date>2003</date><risdate>2003</risdate><volume>27</volume><issue>1</issue><spage>58</spage><epage>64</epage><pages>58-64</pages><issn>0147-5185</issn><eissn>1532-0979</eissn><coden>AJSPDX</coden><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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12502928</pmid><doi>10.1097/00000478-200301000-00007</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Biomarkers, Tumor - metabolism Blotting, Western Dermatology Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Hemangioendothelioma, Epithelioid - blood supply Hemangioendothelioma, Epithelioid - metabolism Hemangioendothelioma, Epithelioid - pathology Hemangioma - blood supply Hemangioma - metabolism Hemangioma - pathology Hemangiosarcoma - blood supply Hemangiosarcoma - metabolism Hemangiosarcoma - pathology Histocytological Preparation Techniques Humans Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Medical sciences Miscellaneous. Technology Neoplasm Proteins - metabolism Neoplasms, Vascular Tissue - blood supply Neoplasms, Vascular Tissue - metabolism Neoplasms, Vascular Tissue - pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Rabbits Sarcoma, Kaposi - blood supply Sarcoma, Kaposi - metabolism Sarcoma, Kaposi - pathology Sensitivity and Specificity Tacrolimus Binding Protein 1A - analysis Tacrolimus Binding Protein 1A - biosynthesis Tumors of the skin and soft tissue. Premalignant lesions Vascular Neoplasms - blood supply Vascular Neoplasms - metabolism Vascular Neoplasms - pathology |
title | Expression of FKBP12 in benign and malignant vascular endothelium: An immunohistochemical study on conventional sections and tissue microarrays |
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