Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy
The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value...
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| Veröffentlicht in: | The journal of pathology. Clinical research 2019-01, Vol.5 (1), p.53-62 |
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| creator | Schuster, Cornelia Akslen, Lars A Stokowy, Tomasz Straume, Oddbjørn |
| description | The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High‐serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin‐1β, and urokinase‐type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy. |
| doi_str_mv | 10.1002/cjp2.116 |
| format | Article |
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Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High‐serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin‐1β, and urokinase‐type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy.</description><identifier>ISSN: 2056-4538</identifier><identifier>EISSN: 2056-4538</identifier><identifier>DOI: 10.1002/cjp2.116</identifier><identifier>PMID: 30225999</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Activin ; Activin A ; Angiogenesis ; Bevacizumab ; bevacizumab monotherapy ; Biomarkers ; Chemotherapy ; Disease control ; Grants ; IL1β ; Immunohistochemistry ; Immunotherapy ; Melanoma ; Metastases ; Metastasis ; metastatic melanoma ; Microvasculature ; Monoclonal antibodies ; Original ; Ovarian cancer ; paraffin embedded tissue ; Patients ; predictive marker ; Protein arrays ; Protein expression ; Proteins ; serum ; Skin cancer ; Studies ; Targeted cancer therapy ; Tumors ; U-Plasminogen activator ; uPAR ; Vascular endothelial growth factor</subject><ispartof>The journal of pathology. Clinical research, 2019-01, Vol.5 (1), p.53-62</ispartof><rights>2018 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). 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Clinical research</title><addtitle>J Pathol Clin Res</addtitle><description>The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High‐serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin‐1β, and urokinase‐type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy.</description><subject>Activin</subject><subject>Activin A</subject><subject>Angiogenesis</subject><subject>Bevacizumab</subject><subject>bevacizumab monotherapy</subject><subject>Biomarkers</subject><subject>Chemotherapy</subject><subject>Disease control</subject><subject>Grants</subject><subject>IL1β</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Melanoma</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>metastatic melanoma</subject><subject>Microvasculature</subject><subject>Monoclonal antibodies</subject><subject>Original</subject><subject>Ovarian cancer</subject><subject>paraffin embedded tissue</subject><subject>Patients</subject><subject>predictive marker</subject><subject>Protein arrays</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>serum</subject><subject>Skin cancer</subject><subject>Studies</subject><subject>Targeted cancer therapy</subject><subject>Tumors</subject><subject>U-Plasminogen activator</subject><subject>uPAR</subject><subject>Vascular endothelial growth factor</subject><issn>2056-4538</issn><issn>2056-4538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc1q3DAUhUVoSUIayBMUQTfdONW_x5tCGdImJdAssheyfD2jwZYcSZ4wffpqmCRMC13di_RxOOcehK4ouaaEsC92M7FrStUJOmdEqkpIvnh3tJ-hy5Q2hBAqKamZOEVnnDAmm6Y5R08PETpns9sC3pphBhx6bPzKhRV4Z_EUQwbnE3YeTyY78DnhZ5fXeIRsUi5PtqyD8WE0OEcwGboD0MLWWPd7Hk2Lx-BDXkM00-4Det-bIcHly7xAj99vHpe31f2vH3fLb_eVFUqpihulmBHGtoJI2YoyhVC9bITseN8RQQUnohddzTh0vF700tYtZZ0SvC2xL9DXg-w0tyN0thiPZtBTdKOJOx2M03__eLfWq7DVitOaLVQR-PwiEMPTDCnr0SULQ4kKYU6aUdJwVjdcFPTTP-gmzNGXdJqxpty6kepI0MaQUoT-zQwlet-k3jepS5MF_Xhs_g187a0A1QF4dgPs_iuklz8f2F7wD2r_qWc</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Schuster, Cornelia</creator><creator>Akslen, Lars A</creator><creator>Stokowy, Tomasz</creator><creator>Straume, Oddbjørn</creator><general>John Wiley & Sons, Inc</general><scope>24P</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2665-9527</orcidid></search><sort><creationdate>201901</creationdate><title>Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy</title><author>Schuster, Cornelia ; Akslen, Lars A ; Stokowy, Tomasz ; Straume, Oddbjørn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4666-3a662a4acb4055b4cb4446f5945d3fd0414304f4d723ed378f5c7b12d643b453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Activin</topic><topic>Activin A</topic><topic>Angiogenesis</topic><topic>Bevacizumab</topic><topic>bevacizumab monotherapy</topic><topic>Biomarkers</topic><topic>Chemotherapy</topic><topic>Disease control</topic><topic>Grants</topic><topic>IL1β</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Melanoma</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>metastatic melanoma</topic><topic>Microvasculature</topic><topic>Monoclonal antibodies</topic><topic>Original</topic><topic>Ovarian cancer</topic><topic>paraffin embedded tissue</topic><topic>Patients</topic><topic>predictive marker</topic><topic>Protein arrays</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>serum</topic><topic>Skin cancer</topic><topic>Studies</topic><topic>Targeted cancer therapy</topic><topic>Tumors</topic><topic>U-Plasminogen activator</topic><topic>uPAR</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schuster, Cornelia</creatorcontrib><creatorcontrib>Akslen, Lars A</creatorcontrib><creatorcontrib>Stokowy, Tomasz</creatorcontrib><creatorcontrib>Straume, Oddbjørn</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of pathology. Clinical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schuster, Cornelia</au><au>Akslen, Lars A</au><au>Stokowy, Tomasz</au><au>Straume, Oddbjørn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy</atitle><jtitle>The journal of pathology. Clinical research</jtitle><addtitle>J Pathol Clin Res</addtitle><date>2019-01</date><risdate>2019</risdate><volume>5</volume><issue>1</issue><spage>53</spage><epage>62</epage><pages>53-62</pages><issn>2056-4538</issn><eissn>2056-4538</eissn><abstract>The incidence of malignant melanoma is rising worldwide and survival for metastatic disease is still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise treatment for this patient group. In this study, we investigated the predictive value of 60 angiogenic factors in patients with metastatic melanoma treated with the anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five patients were included in a clinical phase II trial and baseline serum samples were analysed by multiplex protein array. High‐serum concentration of Activin A was significantly associated with objective response (OR) to treatment (p = 0.014). Candidate proteins that indicated a borderline association with treatment response were further investigated by immunohistochemistry. Strong expression of Activin A, interleukin‐1β, and urokinase‐type plasminogen activator receptor in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p = 0.007, respectively), as well as with markers of activated angiogenesis, such as higher number of proliferating vessels and the presence of glomeruloid microvascular proliferations. Our findings indicate that these proteins may be potential predictive markers for treatment with bevacizumab monotherapy.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>30225999</pmid><doi>10.1002/cjp2.116</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2665-9527</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Activin Activin A Angiogenesis Bevacizumab bevacizumab monotherapy Biomarkers Chemotherapy Disease control Grants IL1β Immunohistochemistry Immunotherapy Melanoma Metastases Metastasis metastatic melanoma Microvasculature Monoclonal antibodies Original Ovarian cancer paraffin embedded tissue Patients predictive marker Protein arrays Protein expression Proteins serum Skin cancer Studies Targeted cancer therapy Tumors U-Plasminogen activator uPAR Vascular endothelial growth factor |
| title | Predictive value of angiogenic proteins in patients with metastatic melanoma treated with bevacizumab monotherapy |
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