Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group
Purpose Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentra...
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| Veröffentlicht in: | European journal of nuclear medicine and molecular imaging 2016-03, Vol.43 (3), p.474-481 |
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| creator | Temple, William Mendelsohn, Lori Kim, Grace E. Nekritz, Erin Gustafson, W. Clay Lin, Lawrence Giacomini, Kathy Naranjo, Arlene Van Ryn, Collin Yanik, Gregory A. Kreissman, Susan G. Hogarty, Michael Matthay, Katherine K. DuBois, Steven G. |
| description | Purpose
Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.
Methods
We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.
Results
Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (
n
= 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in
MYCN
amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45;
p
= 0.04). VMAT1 expression did not correlate with MIBG avidity.
Conclusion
VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG. |
| doi_str_mv | 10.1007/s00259-015-3179-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4733400</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1761470117</sourcerecordid><originalsourceid>FETCH-LOGICAL-c573t-d28345baf87bb1f3c1d3ca48e3e2b14636ed799590f7e7444e0b63c40e387fdc3</originalsourceid><addsrcrecordid>eNqNks9u1DAQhyMEon_gAbggS1w4NGDHTuxwqAQrWCoV9QJcLceZ7Lpy7GA7pXvjNXgQXognwdstq4KExMmW5ptv7NGvKJ4Q_IJgzF9GjKu6LTGpS0p4W1b3ikPSkLbkWLT393eOD4qjGC8xJqIS7cPioGooFbnjsPjxGaLRs1UBjd55NRoHKAXl4uRDgoCm4BMYh-B6ChCj8Q5pHwJYlSCiryatkbbGGa0sGkClOVMnKM2jD6gz3vrV5gQp16MPZ2-WSF2Z3qQNykIHc_CdVTH5Ub1CCgXYjkRD8CNKa0CLtbF9APfz2_eILpy-caFl8PP0qHgwKBvh8e15XHx69_bj4n15frE8W7w-L3XNaSr7SlBWd2oQvOvIQDXpqVZMAIWqI6yhDfS8besWDxw4Ywxw11DNMFDBh17T4-J0553mboReg8ursXIKZlRhI70y8s-KM2u58leScUoZxlnw_FYQ_JcZYpKjiRqsVQ78HCXhTd0KJlr-PyhhHBOyRZ_9hV76Obi8iRsKM9JUJFNkR-ngYwww7N9NsNzmR-7yI3N-5DY_sso9T-9-eN_xOzAZqHZAzCW3gnBn9D-tvwA2TtZt</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1761041621</pqid></control><display><type>article</type><title>Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Temple, William ; Mendelsohn, Lori ; Kim, Grace E. ; Nekritz, Erin ; Gustafson, W. Clay ; Lin, Lawrence ; Giacomini, Kathy ; Naranjo, Arlene ; Van Ryn, Collin ; Yanik, Gregory A. ; Kreissman, Susan G. ; Hogarty, Michael ; Matthay, Katherine K. ; DuBois, Steven G.</creator><creatorcontrib>Temple, William ; Mendelsohn, Lori ; Kim, Grace E. ; Nekritz, Erin ; Gustafson, W. Clay ; Lin, Lawrence ; Giacomini, Kathy ; Naranjo, Arlene ; Van Ryn, Collin ; Yanik, Gregory A. ; Kreissman, Susan G. ; Hogarty, Michael ; Matthay, Katherine K. ; DuBois, Steven G.</creatorcontrib><description>Purpose
Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.
Methods
We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.
Results
Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (
n
= 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in
MYCN
amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45;
p
= 0.04). VMAT1 expression did not correlate with MIBG avidity.
Conclusion
VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-015-3179-2</identifier><identifier>PMID: 26338179</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>3-Iodobenzylguanidine - chemistry ; Cancer ; Cardiology ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Imaging ; Immunohistochemistry ; Infant ; Medicine ; Medicine & Public Health ; Molecular biology ; Neoplasm Metastasis ; Neuroblastoma - therapy ; Norepinephrine Plasma Membrane Transport Proteins - metabolism ; Nuclear Medicine ; Oncology ; Original Article ; Orthopedics ; Pediatrics ; Proteins ; Radiology ; Retrospective Studies ; Treatment Outcome ; Tumors ; Vesicular Monoamine Transport Proteins - metabolism</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2016-03, Vol.43 (3), p.474-481</ispartof><rights>Springer-Verlag Berlin Heidelberg 2015</rights><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-d28345baf87bb1f3c1d3ca48e3e2b14636ed799590f7e7444e0b63c40e387fdc3</citedby><cites>FETCH-LOGICAL-c573t-d28345baf87bb1f3c1d3ca48e3e2b14636ed799590f7e7444e0b63c40e387fdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00259-015-3179-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00259-015-3179-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26338179$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Temple, William</creatorcontrib><creatorcontrib>Mendelsohn, Lori</creatorcontrib><creatorcontrib>Kim, Grace E.</creatorcontrib><creatorcontrib>Nekritz, Erin</creatorcontrib><creatorcontrib>Gustafson, W. Clay</creatorcontrib><creatorcontrib>Lin, Lawrence</creatorcontrib><creatorcontrib>Giacomini, Kathy</creatorcontrib><creatorcontrib>Naranjo, Arlene</creatorcontrib><creatorcontrib>Van Ryn, Collin</creatorcontrib><creatorcontrib>Yanik, Gregory A.</creatorcontrib><creatorcontrib>Kreissman, Susan G.</creatorcontrib><creatorcontrib>Hogarty, Michael</creatorcontrib><creatorcontrib>Matthay, Katherine K.</creatorcontrib><creatorcontrib>DuBois, Steven G.</creatorcontrib><title>Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.
Methods
We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.
Results
Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (
n
= 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in
MYCN
amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45;
p
= 0.04). VMAT1 expression did not correlate with MIBG avidity.
Conclusion
VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG.</description><subject>3-Iodobenzylguanidine - chemistry</subject><subject>Cancer</subject><subject>Cardiology</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Imaging</subject><subject>Immunohistochemistry</subject><subject>Infant</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular biology</subject><subject>Neoplasm Metastasis</subject><subject>Neuroblastoma - therapy</subject><subject>Norepinephrine Plasma Membrane Transport Proteins - metabolism</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Pediatrics</subject><subject>Proteins</subject><subject>Radiology</subject><subject>Retrospective Studies</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Vesicular Monoamine Transport Proteins - metabolism</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNks9u1DAQhyMEon_gAbggS1w4NGDHTuxwqAQrWCoV9QJcLceZ7Lpy7GA7pXvjNXgQXognwdstq4KExMmW5ptv7NGvKJ4Q_IJgzF9GjKu6LTGpS0p4W1b3ikPSkLbkWLT393eOD4qjGC8xJqIS7cPioGooFbnjsPjxGaLRs1UBjd55NRoHKAXl4uRDgoCm4BMYh-B6ChCj8Q5pHwJYlSCiryatkbbGGa0sGkClOVMnKM2jD6gz3vrV5gQp16MPZ2-WSF2Z3qQNykIHc_CdVTH5Ub1CCgXYjkRD8CNKa0CLtbF9APfz2_eILpy-caFl8PP0qHgwKBvh8e15XHx69_bj4n15frE8W7w-L3XNaSr7SlBWd2oQvOvIQDXpqVZMAIWqI6yhDfS8besWDxw4Ywxw11DNMFDBh17T4-J0553mboReg8ursXIKZlRhI70y8s-KM2u58leScUoZxlnw_FYQ_JcZYpKjiRqsVQ78HCXhTd0KJlr-PyhhHBOyRZ_9hV76Obi8iRsKM9JUJFNkR-ngYwww7N9NsNzmR-7yI3N-5DY_sso9T-9-eN_xOzAZqHZAzCW3gnBn9D-tvwA2TtZt</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Temple, William</creator><creator>Mendelsohn, Lori</creator><creator>Kim, Grace E.</creator><creator>Nekritz, Erin</creator><creator>Gustafson, W. Clay</creator><creator>Lin, Lawrence</creator><creator>Giacomini, Kathy</creator><creator>Naranjo, Arlene</creator><creator>Van Ryn, Collin</creator><creator>Yanik, Gregory A.</creator><creator>Kreissman, Susan G.</creator><creator>Hogarty, Michael</creator><creator>Matthay, Katherine K.</creator><creator>DuBois, Steven G.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</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>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20160301</creationdate><title>Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group</title><author>Temple, William ; Mendelsohn, Lori ; Kim, Grace E. ; Nekritz, Erin ; Gustafson, W. Clay ; Lin, Lawrence ; Giacomini, Kathy ; Naranjo, Arlene ; Van Ryn, Collin ; Yanik, Gregory A. ; Kreissman, Susan G. ; Hogarty, Michael ; Matthay, Katherine K. ; DuBois, Steven G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-d28345baf87bb1f3c1d3ca48e3e2b14636ed799590f7e7444e0b63c40e387fdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3-Iodobenzylguanidine - chemistry</topic><topic>Cancer</topic><topic>Cardiology</topic><topic>Cell Line, Tumor</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Imaging</topic><topic>Immunohistochemistry</topic><topic>Infant</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular biology</topic><topic>Neoplasm Metastasis</topic><topic>Neuroblastoma - therapy</topic><topic>Norepinephrine Plasma Membrane Transport Proteins - metabolism</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Pediatrics</topic><topic>Proteins</topic><topic>Radiology</topic><topic>Retrospective Studies</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Vesicular Monoamine Transport Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Temple, William</creatorcontrib><creatorcontrib>Mendelsohn, Lori</creatorcontrib><creatorcontrib>Kim, Grace E.</creatorcontrib><creatorcontrib>Nekritz, Erin</creatorcontrib><creatorcontrib>Gustafson, W. Clay</creatorcontrib><creatorcontrib>Lin, Lawrence</creatorcontrib><creatorcontrib>Giacomini, Kathy</creatorcontrib><creatorcontrib>Naranjo, Arlene</creatorcontrib><creatorcontrib>Van Ryn, Collin</creatorcontrib><creatorcontrib>Yanik, Gregory A.</creatorcontrib><creatorcontrib>Kreissman, Susan G.</creatorcontrib><creatorcontrib>Hogarty, Michael</creatorcontrib><creatorcontrib>Matthay, Katherine K.</creatorcontrib><creatorcontrib>DuBois, Steven G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of nuclear medicine and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Temple, William</au><au>Mendelsohn, Lori</au><au>Kim, Grace E.</au><au>Nekritz, Erin</au><au>Gustafson, W. Clay</au><au>Lin, Lawrence</au><au>Giacomini, Kathy</au><au>Naranjo, Arlene</au><au>Van Ryn, Collin</au><au>Yanik, Gregory A.</au><au>Kreissman, Susan G.</au><au>Hogarty, Michael</au><au>Matthay, Katherine K.</au><au>DuBois, Steven G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><addtitle>Eur J Nucl Med Mol Imaging</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>43</volume><issue>3</issue><spage>474</spage><epage>481</epage><pages>474-481</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose
Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.
Methods
We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.
Results
Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (
n
= 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in
MYCN
amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45;
p
= 0.04). VMAT1 expression did not correlate with MIBG avidity.
Conclusion
VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26338179</pmid><doi>10.1007/s00259-015-3179-2</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1619-7070 |
| ispartof | European journal of nuclear medicine and molecular imaging, 2016-03, Vol.43 (3), p.474-481 |
| issn | 1619-7070 1619-7089 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4733400 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | 3-Iodobenzylguanidine - chemistry Cancer Cardiology Cell Line, Tumor Gene Expression Profiling Gene Expression Regulation Gene Expression Regulation, Neoplastic Humans Imaging Immunohistochemistry Infant Medicine Medicine & Public Health Molecular biology Neoplasm Metastasis Neuroblastoma - therapy Norepinephrine Plasma Membrane Transport Proteins - metabolism Nuclear Medicine Oncology Original Article Orthopedics Pediatrics Proteins Radiology Retrospective Studies Treatment Outcome Tumors Vesicular Monoamine Transport Proteins - metabolism |
| title | Vesicular monoamine transporter protein expression correlates with clinical features, tumor biology, and MIBG avidity in neuroblastoma: a report from the Children’s Oncology Group |
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