MYC amplification in angiosarcoma depends on etiological/clinical subgroups – Diagnostic and prognostic value
Angiosarcomas (AS) are rare and heterogeneous malignant vascular tumors with a dismal prognosis. We undertook a retrospective study of AS cases with the intent of elucidating the prevalence of MYC amplification amongst different etiological/clinical subgroups and identifying MYC's potential as...
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Veröffentlicht in: | Annals of diagnostic pathology 2023-04, Vol.63, p.152096-152096, Article 152096 |
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creator | Hogeboom-Gimeno, A.G. van Ravensteijn, S.G. Desar, I.M.E. Hillebrandt-Roeffen, M.H.S. van Cleef, P.H.J. Bonenkamp, J.J. Flucke, U. Versleijen-Jonkers, Y.M.H. |
description | Angiosarcomas (AS) are rare and heterogeneous malignant vascular tumors with a dismal prognosis. We undertook a retrospective study of AS cases with the intent of elucidating the prevalence of MYC amplification amongst different etiological/clinical subgroups and identifying MYC's potential as a prognostic biomarker.
Retrospective collection of data and tumor samples from 110 patients diagnosed with AS in the Netherlands was conducted. Histopathological review and investigation of MYC gene amplification and MYC protein overexpression (using fluorescent in situ hybridization and immunohistochemistry, respectively) was performed.
MYC amplification was identified in 50.9 % of cases and predominantly present in secondary AS (sAS) (especially radiotherapy-associated and Stewart-Treves AS, both 92.9 %). Within the primary AS (pAS) subgroup, skin non-UV-associated AS (69.2 %) and primary breast AS (29.4 %) demonstrated MYC amplification. MYC protein overexpression was observed in 47.7 % of all tumors with an overall sensitivity and specificity of 75 % and 81 % respectively. There was no significant difference in median overall survival (OS) between patients with MYC and non-MYC amplified AS. Patients with AS displaying MYC protein overexpression had significantly shorter OS than those without (p = 0.028).
Although MYC amplification is characteristic for secondary radiotherapy-associated and Stewart-Treves AS, it is not exclusive to these groups and can also be found in a subset of pAS. Overall concordance of FISH and IHC is rather poor. Only primary breast AS showed 100 % concordance. Therefore MYC expression as surrogate marker should be used with caution. The role of MYC/MYC as a prognostic indicator is undefined, however resulting tailored treatment options could be considered.
•MYC is mainly amplified in radiotherapy-associated and Stewart-Treves angiosarcoma.•MYC is mainly amplified in non-UV-associated compared to UV-associated angiosarcoma.•Concordance between MYC FISH and IHC is rather poor.•MYC expression correlates with shorter overall survival in angiosarcoma. |
doi_str_mv | 10.1016/j.anndiagpath.2022.152096 |
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Retrospective collection of data and tumor samples from 110 patients diagnosed with AS in the Netherlands was conducted. Histopathological review and investigation of MYC gene amplification and MYC protein overexpression (using fluorescent in situ hybridization and immunohistochemistry, respectively) was performed.
MYC amplification was identified in 50.9 % of cases and predominantly present in secondary AS (sAS) (especially radiotherapy-associated and Stewart-Treves AS, both 92.9 %). Within the primary AS (pAS) subgroup, skin non-UV-associated AS (69.2 %) and primary breast AS (29.4 %) demonstrated MYC amplification. MYC protein overexpression was observed in 47.7 % of all tumors with an overall sensitivity and specificity of 75 % and 81 % respectively. There was no significant difference in median overall survival (OS) between patients with MYC and non-MYC amplified AS. Patients with AS displaying MYC protein overexpression had significantly shorter OS than those without (p = 0.028).
Although MYC amplification is characteristic for secondary radiotherapy-associated and Stewart-Treves AS, it is not exclusive to these groups and can also be found in a subset of pAS. Overall concordance of FISH and IHC is rather poor. Only primary breast AS showed 100 % concordance. Therefore MYC expression as surrogate marker should be used with caution. The role of MYC/MYC as a prognostic indicator is undefined, however resulting tailored treatment options could be considered.
•MYC is mainly amplified in radiotherapy-associated and Stewart-Treves angiosarcoma.•MYC is mainly amplified in non-UV-associated compared to UV-associated angiosarcoma.•Concordance between MYC FISH and IHC is rather poor.•MYC expression correlates with shorter overall survival in angiosarcoma.</description><identifier>ISSN: 1092-9134</identifier><identifier>EISSN: 1532-8198</identifier><identifier>DOI: 10.1016/j.anndiagpath.2022.152096</identifier><identifier>PMID: 36610315</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angiosarcoma ; Diagnostic ; Gene Amplification ; Genes, myc ; Hemangiosarcoma ; Humans ; Immunohistochemistry ; MYC amplification ; Prognosis ; Prognostic ; Subgroups</subject><ispartof>Annals of diagnostic pathology, 2023-04, Vol.63, p.152096-152096, Article 152096</ispartof><rights>2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-11e8b6dfc85501c670d8748d1fd6ca12e12ae98687076f5ed0f0e32ded36b0c03</citedby><cites>FETCH-LOGICAL-c428t-11e8b6dfc85501c670d8748d1fd6ca12e12ae98687076f5ed0f0e32ded36b0c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.anndiagpath.2022.152096$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36610315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hogeboom-Gimeno, A.G.</creatorcontrib><creatorcontrib>van Ravensteijn, S.G.</creatorcontrib><creatorcontrib>Desar, I.M.E.</creatorcontrib><creatorcontrib>Hillebrandt-Roeffen, M.H.S.</creatorcontrib><creatorcontrib>van Cleef, P.H.J.</creatorcontrib><creatorcontrib>Bonenkamp, J.J.</creatorcontrib><creatorcontrib>Flucke, U.</creatorcontrib><creatorcontrib>Versleijen-Jonkers, Y.M.H.</creatorcontrib><title>MYC amplification in angiosarcoma depends on etiological/clinical subgroups – Diagnostic and prognostic value</title><title>Annals of diagnostic pathology</title><addtitle>Ann Diagn Pathol</addtitle><description>Angiosarcomas (AS) are rare and heterogeneous malignant vascular tumors with a dismal prognosis. We undertook a retrospective study of AS cases with the intent of elucidating the prevalence of MYC amplification amongst different etiological/clinical subgroups and identifying MYC's potential as a prognostic biomarker.
Retrospective collection of data and tumor samples from 110 patients diagnosed with AS in the Netherlands was conducted. Histopathological review and investigation of MYC gene amplification and MYC protein overexpression (using fluorescent in situ hybridization and immunohistochemistry, respectively) was performed.
MYC amplification was identified in 50.9 % of cases and predominantly present in secondary AS (sAS) (especially radiotherapy-associated and Stewart-Treves AS, both 92.9 %). Within the primary AS (pAS) subgroup, skin non-UV-associated AS (69.2 %) and primary breast AS (29.4 %) demonstrated MYC amplification. MYC protein overexpression was observed in 47.7 % of all tumors with an overall sensitivity and specificity of 75 % and 81 % respectively. There was no significant difference in median overall survival (OS) between patients with MYC and non-MYC amplified AS. Patients with AS displaying MYC protein overexpression had significantly shorter OS than those without (p = 0.028).
Although MYC amplification is characteristic for secondary radiotherapy-associated and Stewart-Treves AS, it is not exclusive to these groups and can also be found in a subset of pAS. Overall concordance of FISH and IHC is rather poor. Only primary breast AS showed 100 % concordance. Therefore MYC expression as surrogate marker should be used with caution. The role of MYC/MYC as a prognostic indicator is undefined, however resulting tailored treatment options could be considered.
•MYC is mainly amplified in radiotherapy-associated and Stewart-Treves angiosarcoma.•MYC is mainly amplified in non-UV-associated compared to UV-associated angiosarcoma.•Concordance between MYC FISH and IHC is rather poor.•MYC expression correlates with shorter overall survival in angiosarcoma.</description><subject>Angiosarcoma</subject><subject>Diagnostic</subject><subject>Gene Amplification</subject><subject>Genes, myc</subject><subject>Hemangiosarcoma</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>MYC amplification</subject><subject>Prognosis</subject><subject>Prognostic</subject><subject>Subgroups</subject><issn>1092-9134</issn><issn>1532-8198</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkL1u2zAQgIkiQeMmfYWC2bLI5lEWRY2B06QFXGRJhkwETZ5cGhKpkpKBbn2HvmGeJDScFBk78Yj77u8j5BLYHBiIxW6uvbdObwc9_pxzxvkcKs4a8YHMoCp5IaGRJzlmDS8aKJdn5FNKO8YAllX9kZyVQgAroZqR8ONpRXU_dK51Ro8ueOo81X7rQtLRhF5TiwN6m2hOYQa6sM1ktzCd84eApmmzjWEaEn3-85fe5LV8SKMzuYulQwxv373uJrwgp63uEn5-fc_J4-3Xh9W3Yn1_9311vS7MksuxAEC5EbY1sqoYGFEzK-ultNBaYTRwBK6xkULWrBZthZa1DEtu0ZZiwwwrz8nVsW9e4NeEaVS9Swa7TnsMU1K8FtkRFxXPaHNETQwpRWzVEF2v428FTB18q51651sdfKuj71z75XXMtOnR_qt8E5yB1RHAfOzeYVTJOPQGrYtoRmWD-48xL_1_mhY</recordid><startdate>202304</startdate><enddate>202304</enddate><creator>Hogeboom-Gimeno, A.G.</creator><creator>van Ravensteijn, S.G.</creator><creator>Desar, I.M.E.</creator><creator>Hillebrandt-Roeffen, M.H.S.</creator><creator>van Cleef, P.H.J.</creator><creator>Bonenkamp, J.J.</creator><creator>Flucke, U.</creator><creator>Versleijen-Jonkers, Y.M.H.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202304</creationdate><title>MYC amplification in angiosarcoma depends on etiological/clinical subgroups – Diagnostic and prognostic value</title><author>Hogeboom-Gimeno, A.G. ; van Ravensteijn, S.G. ; Desar, I.M.E. ; Hillebrandt-Roeffen, M.H.S. ; van Cleef, P.H.J. ; Bonenkamp, J.J. ; Flucke, U. ; Versleijen-Jonkers, Y.M.H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-11e8b6dfc85501c670d8748d1fd6ca12e12ae98687076f5ed0f0e32ded36b0c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Angiosarcoma</topic><topic>Diagnostic</topic><topic>Gene Amplification</topic><topic>Genes, myc</topic><topic>Hemangiosarcoma</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>MYC amplification</topic><topic>Prognosis</topic><topic>Prognostic</topic><topic>Subgroups</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hogeboom-Gimeno, A.G.</creatorcontrib><creatorcontrib>van Ravensteijn, S.G.</creatorcontrib><creatorcontrib>Desar, I.M.E.</creatorcontrib><creatorcontrib>Hillebrandt-Roeffen, M.H.S.</creatorcontrib><creatorcontrib>van Cleef, P.H.J.</creatorcontrib><creatorcontrib>Bonenkamp, J.J.</creatorcontrib><creatorcontrib>Flucke, U.</creatorcontrib><creatorcontrib>Versleijen-Jonkers, Y.M.H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of diagnostic pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hogeboom-Gimeno, A.G.</au><au>van Ravensteijn, S.G.</au><au>Desar, I.M.E.</au><au>Hillebrandt-Roeffen, M.H.S.</au><au>van Cleef, P.H.J.</au><au>Bonenkamp, J.J.</au><au>Flucke, U.</au><au>Versleijen-Jonkers, Y.M.H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MYC amplification in angiosarcoma depends on etiological/clinical subgroups – Diagnostic and prognostic value</atitle><jtitle>Annals of diagnostic pathology</jtitle><addtitle>Ann Diagn Pathol</addtitle><date>2023-04</date><risdate>2023</risdate><volume>63</volume><spage>152096</spage><epage>152096</epage><pages>152096-152096</pages><artnum>152096</artnum><issn>1092-9134</issn><eissn>1532-8198</eissn><abstract>Angiosarcomas (AS) are rare and heterogeneous malignant vascular tumors with a dismal prognosis. We undertook a retrospective study of AS cases with the intent of elucidating the prevalence of MYC amplification amongst different etiological/clinical subgroups and identifying MYC's potential as a prognostic biomarker.
Retrospective collection of data and tumor samples from 110 patients diagnosed with AS in the Netherlands was conducted. Histopathological review and investigation of MYC gene amplification and MYC protein overexpression (using fluorescent in situ hybridization and immunohistochemistry, respectively) was performed.
MYC amplification was identified in 50.9 % of cases and predominantly present in secondary AS (sAS) (especially radiotherapy-associated and Stewart-Treves AS, both 92.9 %). Within the primary AS (pAS) subgroup, skin non-UV-associated AS (69.2 %) and primary breast AS (29.4 %) demonstrated MYC amplification. MYC protein overexpression was observed in 47.7 % of all tumors with an overall sensitivity and specificity of 75 % and 81 % respectively. There was no significant difference in median overall survival (OS) between patients with MYC and non-MYC amplified AS. Patients with AS displaying MYC protein overexpression had significantly shorter OS than those without (p = 0.028).
Although MYC amplification is characteristic for secondary radiotherapy-associated and Stewart-Treves AS, it is not exclusive to these groups and can also be found in a subset of pAS. Overall concordance of FISH and IHC is rather poor. Only primary breast AS showed 100 % concordance. Therefore MYC expression as surrogate marker should be used with caution. The role of MYC/MYC as a prognostic indicator is undefined, however resulting tailored treatment options could be considered.
•MYC is mainly amplified in radiotherapy-associated and Stewart-Treves angiosarcoma.•MYC is mainly amplified in non-UV-associated compared to UV-associated angiosarcoma.•Concordance between MYC FISH and IHC is rather poor.•MYC expression correlates with shorter overall survival in angiosarcoma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36610315</pmid><doi>10.1016/j.anndiagpath.2022.152096</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiosarcoma Diagnostic Gene Amplification Genes, myc Hemangiosarcoma Humans Immunohistochemistry MYC amplification Prognosis Prognostic Subgroups |
title | MYC amplification in angiosarcoma depends on etiological/clinical subgroups – Diagnostic and prognostic value |
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