Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma
Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related di...
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| Veröffentlicht in: | Clinical cancer research 2012-09, Vol.18 (17), p.4702-4712 |
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| creator | CHUN CHAO SILVERBERG, Michael J MARTINEZ-MAZA, Otoniel CHI, Margaret ABRAMS, Donald I HAQUE, Reina ZHA, Hongbin D MCGUIRE, Michelle LANFANG XU SAID, Jonathan |
| description | Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.
HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.
Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].
Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs. |
| doi_str_mv | 10.1158/1078-0432.ccr-11-3169 |
| format | Article |
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HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.
Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].
Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.ccr-11-3169</identifier><identifier>PMID: 22711707</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Acquired Immunodeficiency Syndrome - complications ; Acquired Immunodeficiency Syndrome - metabolism ; Acquired Immunodeficiency Syndrome - pathology ; Adaptor Proteins, Signal Transducing - metabolism ; Antineoplastic agents ; Apoptosis ; B7-1 Antigen - metabolism ; Biological and medical sciences ; Cell Cycle Proteins - metabolism ; DNA-Binding Proteins - metabolism ; Epstein-Barr virus ; Epstein-Barr Virus Infections - complications ; Epstein-Barr Virus Infections - metabolism ; Epstein-Barr Virus Infections - pathology ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Hematologic and hematopoietic diseases ; Herpesvirus 4, Human - isolation & purification ; Herpesvirus 4, Human - pathogenicity ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; In Situ Hybridization ; Infectious diseases ; Kaplan-Meier Estimate ; Ki-1 Antigen - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; LIM Domain Proteins - metabolism ; Lymphoma, AIDS-Related - complications ; Lymphoma, AIDS-Related - metabolism ; Lymphoma, AIDS-Related - pathology ; Lymphoma, Large B-Cell, Diffuse - complications ; Lymphoma, Large B-Cell, Diffuse - metabolism ; Lymphoma, Large B-Cell, Diffuse - virology ; Medical sciences ; NF-kappa B - metabolism ; Pharmacology. Drug treatments ; Positive Regulatory Domain I-Binding Factor 1 ; Prognosis ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Repressor Proteins - metabolism ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids</subject><ispartof>Clinical cancer research, 2012-09, Vol.18 (17), p.4702-4712</ispartof><rights>2015 INIST-CNRS</rights><rights>2012 AACR.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-f71e72e280262eae7f1480430e6e7f0775b523fde2e47fe5f31b6f96aa82a593</citedby><cites>FETCH-LOGICAL-c540t-f71e72e280262eae7f1480430e6e7f0775b523fde2e47fe5f31b6f96aa82a593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26346022$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22711707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHUN CHAO</creatorcontrib><creatorcontrib>SILVERBERG, Michael J</creatorcontrib><creatorcontrib>MARTINEZ-MAZA, Otoniel</creatorcontrib><creatorcontrib>CHI, Margaret</creatorcontrib><creatorcontrib>ABRAMS, Donald I</creatorcontrib><creatorcontrib>HAQUE, Reina</creatorcontrib><creatorcontrib>ZHA, Hongbin D</creatorcontrib><creatorcontrib>MCGUIRE, Michelle</creatorcontrib><creatorcontrib>LANFANG XU</creatorcontrib><creatorcontrib>SAID, Jonathan</creatorcontrib><title>Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.
HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.
Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].
Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.</description><subject>Acquired Immunodeficiency Syndrome - complications</subject><subject>Acquired Immunodeficiency Syndrome - metabolism</subject><subject>Acquired Immunodeficiency Syndrome - pathology</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>B7-1 Antigen - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - complications</subject><subject>Epstein-Barr Virus Infections - metabolism</subject><subject>Epstein-Barr Virus Infections - pathology</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Herpesvirus 4, Human - isolation & purification</subject><subject>Herpesvirus 4, Human - pathogenicity</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunodeficiencies</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>In Situ Hybridization</subject><subject>Infectious diseases</subject><subject>Kaplan-Meier Estimate</subject><subject>Ki-1 Antigen - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>LIM Domain Proteins - metabolism</subject><subject>Lymphoma, AIDS-Related - complications</subject><subject>Lymphoma, AIDS-Related - metabolism</subject><subject>Lymphoma, AIDS-Related - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - complications</subject><subject>Lymphoma, Large B-Cell, Diffuse - metabolism</subject><subject>Lymphoma, Large B-Cell, Diffuse - virology</subject><subject>Medical sciences</subject><subject>NF-kappa B - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Positive Regulatory Domain I-Binding Factor 1</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-6</subject><subject>Repressor Proteins - metabolism</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1vFCEYhSdGY2v1J2i4MfGGyscAMzcmdrvaTbZp0jS9JSz7skVnYIQZ0_57mXS36lWveIHnnHA4VfWeklNKRfOZEtVgUnN2am3ClGJOZfuiOqZCKMyZFC_LfGCOqjc5_yCE1pTUr6sjxhSliqjjalwOeQQf8JlJCd36NGW0Cg7s6GNAJmzR8n5IkPO8jQ6dYQtdh66CjTsI3qJLk35CysgHdLG6xdfQmRG26Nw7N2VAa5N2cFCtH_rhLvbmbfXKmS7Du_16Ut18W94sLvD66vtq8XWNrajJiJ2ioBiwhjDJwIBytG5KHAKyzEQpsRGMuy0wqJUD4TjdSNdKYxpmRMtPqi-PtsO06WFrIYzJdHpIvjfpQUfj9f83wd_pXfyteVNLwWaDT3uDFH9NkEfd-zwnMQHilHX5ayo5aQl_Hi2lCU7bVhVUPKI2xZwTuKcXUaLnbvXcm55704vFdTnSc7dF9-HfOE-qQ5kF-LgHTLamc8kE6_NfTvJaEsb4H0s3rTk</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>CHUN CHAO</creator><creator>SILVERBERG, Michael J</creator><creator>MARTINEZ-MAZA, Otoniel</creator><creator>CHI, Margaret</creator><creator>ABRAMS, Donald I</creator><creator>HAQUE, Reina</creator><creator>ZHA, Hongbin D</creator><creator>MCGUIRE, Michelle</creator><creator>LANFANG XU</creator><creator>SAID, Jonathan</creator><general>American Association for Cancer Research</general><scope>IQODW</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><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20120901</creationdate><title>Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma</title><author>CHUN CHAO ; SILVERBERG, Michael J ; MARTINEZ-MAZA, Otoniel ; CHI, Margaret ; ABRAMS, Donald I ; HAQUE, Reina ; ZHA, Hongbin D ; MCGUIRE, Michelle ; LANFANG XU ; SAID, Jonathan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-f71e72e280262eae7f1480430e6e7f0775b523fde2e47fe5f31b6f96aa82a593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Acquired Immunodeficiency Syndrome - complications</topic><topic>Acquired Immunodeficiency Syndrome - metabolism</topic><topic>Acquired Immunodeficiency Syndrome - pathology</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>B7-1 Antigen - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - complications</topic><topic>Epstein-Barr Virus Infections - metabolism</topic><topic>Epstein-Barr Virus Infections - pathology</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Herpesvirus 4, Human - isolation & purification</topic><topic>Herpesvirus 4, Human - pathogenicity</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunodeficiencies</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>In Situ Hybridization</topic><topic>Infectious diseases</topic><topic>Kaplan-Meier Estimate</topic><topic>Ki-1 Antigen - metabolism</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>LIM Domain Proteins - metabolism</topic><topic>Lymphoma, AIDS-Related - complications</topic><topic>Lymphoma, AIDS-Related - metabolism</topic><topic>Lymphoma, AIDS-Related - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - complications</topic><topic>Lymphoma, Large B-Cell, Diffuse - metabolism</topic><topic>Lymphoma, Large B-Cell, Diffuse - virology</topic><topic>Medical sciences</topic><topic>NF-kappa B - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Positive Regulatory Domain I-Binding Factor 1</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-6</topic><topic>Repressor Proteins - metabolism</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHUN CHAO</creatorcontrib><creatorcontrib>SILVERBERG, Michael J</creatorcontrib><creatorcontrib>MARTINEZ-MAZA, Otoniel</creatorcontrib><creatorcontrib>CHI, Margaret</creatorcontrib><creatorcontrib>ABRAMS, Donald I</creatorcontrib><creatorcontrib>HAQUE, Reina</creatorcontrib><creatorcontrib>ZHA, Hongbin D</creatorcontrib><creatorcontrib>MCGUIRE, Michelle</creatorcontrib><creatorcontrib>LANFANG XU</creatorcontrib><creatorcontrib>SAID, Jonathan</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><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHUN CHAO</au><au>SILVERBERG, Michael J</au><au>MARTINEZ-MAZA, Otoniel</au><au>CHI, Margaret</au><au>ABRAMS, Donald I</au><au>HAQUE, Reina</au><au>ZHA, Hongbin D</au><au>MCGUIRE, Michelle</au><au>LANFANG XU</au><au>SAID, Jonathan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>18</volume><issue>17</issue><spage>4702</spage><epage>4712</epage><pages>4702-4712</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.
HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.
Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].
Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>22711707</pmid><doi>10.1158/1078-0432.ccr-11-3169</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acquired Immunodeficiency Syndrome - complications Acquired Immunodeficiency Syndrome - metabolism Acquired Immunodeficiency Syndrome - pathology Adaptor Proteins, Signal Transducing - metabolism Antineoplastic agents Apoptosis B7-1 Antigen - metabolism Biological and medical sciences Cell Cycle Proteins - metabolism DNA-Binding Proteins - metabolism Epstein-Barr virus Epstein-Barr Virus Infections - complications Epstein-Barr Virus Infections - metabolism Epstein-Barr Virus Infections - pathology Follow-Up Studies Gene Expression Regulation, Neoplastic Hematologic and hematopoietic diseases Herpesvirus 4, Human - isolation & purification Herpesvirus 4, Human - pathogenicity Human immunodeficiency virus Human viral diseases Humans Immunodeficiencies Immunodeficiencies. Immunoglobulinopathies Immunopathology In Situ Hybridization Infectious diseases Kaplan-Meier Estimate Ki-1 Antigen - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis LIM Domain Proteins - metabolism Lymphoma, AIDS-Related - complications Lymphoma, AIDS-Related - metabolism Lymphoma, AIDS-Related - pathology Lymphoma, Large B-Cell, Diffuse - complications Lymphoma, Large B-Cell, Diffuse - metabolism Lymphoma, Large B-Cell, Diffuse - virology Medical sciences NF-kappa B - metabolism Pharmacology. Drug treatments Positive Regulatory Domain I-Binding Factor 1 Prognosis Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-bcl-6 Repressor Proteins - metabolism Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma |
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