Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma
Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemica...
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| Veröffentlicht in: | Clinical cancer research 1999-05, Vol.5 (5), p.1085-1091 |
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| creator | MØLLER, M. B GERDES, A.-M SKJØDT, K MORTENSEN, L. S PEDERSEN, N. T |
| description | Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical
analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the
basis of p53 gene mutation status and immunohistochemically detected p53 and p21 Waf1 expression in 34 lymphomas, we established an immunophenotype (Δp53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry
and was correlated with clinical parameters. Δp53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that Δp53 was
independently associated with treatment failure (relative risk, 3.8; P = 0.001). Δp53 predicted poor survival when analyzing all patients ( P = 0.0001), as well as B-cell ( P = 0.04) and T-cell NHL ( P = 0.000002). In multivariate analysis, Δp53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of Δp53 was highly significant in the low-intermediate-risk
group ( P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Δp53 patients died within
1 year, whereas the median survival of the 28 non-Δp53 patients was 36 months. These results suggest that immunohistochemically
assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients. |
| format | Article |
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analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the
basis of p53 gene mutation status and immunohistochemically detected p53 and p21 Waf1 expression in 34 lymphomas, we established an immunophenotype (Δp53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry
and was correlated with clinical parameters. Δp53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that Δp53 was
independently associated with treatment failure (relative risk, 3.8; P = 0.001). Δp53 predicted poor survival when analyzing all patients ( P = 0.0001), as well as B-cell ( P = 0.04) and T-cell NHL ( P = 0.000002). In multivariate analysis, Δp53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of Δp53 was highly significant in the low-intermediate-risk
group ( P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Δp53 patients died within
1 year, whereas the median survival of the 28 non-Δp53 patients was 36 months. These results suggest that immunohistochemically
assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10353742</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adolescent ; Adult ; Aged ; Apoptosis ; Biological and medical sciences ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins - analysis ; Denmark - epidemiology ; DNA, Neoplasm - genetics ; Exons - genetics ; Female ; Genes, p53 ; Hematologic and hematopoietic diseases ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphoma, B-Cell - chemistry ; Lymphoma, B-Cell - drug therapy ; Lymphoma, B-Cell - genetics ; Lymphoma, B-Cell - mortality ; Lymphoma, T-Cell - chemistry ; Lymphoma, T-Cell - drug therapy ; Lymphoma, T-Cell - genetics ; Lymphoma, T-Cell - mortality ; Male ; Medical sciences ; Middle Aged ; Neoplasm Proteins - deficiency ; Neoplasm Proteins - physiology ; Phenotype ; Prognosis ; Retrospective Studies ; Survival Analysis ; Treatment Failure ; Tumor Suppressor Protein p53 - deficiency ; Tumor Suppressor Protein p53 - physiology</subject><ispartof>Clinical cancer research, 1999-05, Vol.5 (5), p.1085-1091</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1786003$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10353742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MØLLER, M. B</creatorcontrib><creatorcontrib>GERDES, A.-M</creatorcontrib><creatorcontrib>SKJØDT, K</creatorcontrib><creatorcontrib>MORTENSEN, L. S</creatorcontrib><creatorcontrib>PEDERSEN, N. T</creatorcontrib><title>Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical
analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the
basis of p53 gene mutation status and immunohistochemically detected p53 and p21 Waf1 expression in 34 lymphomas, we established an immunophenotype (Δp53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry
and was correlated with clinical parameters. Δp53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that Δp53 was
independently associated with treatment failure (relative risk, 3.8; P = 0.001). Δp53 predicted poor survival when analyzing all patients ( P = 0.0001), as well as B-cell ( P = 0.04) and T-cell NHL ( P = 0.000002). In multivariate analysis, Δp53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of Δp53 was highly significant in the low-intermediate-risk
group ( P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Δp53 patients died within
1 year, whereas the median survival of the 28 non-Δp53 patients was 36 months. These results suggest that immunohistochemically
assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - analysis</subject><subject>Denmark - epidemiology</subject><subject>DNA, Neoplasm - genetics</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>Genes, p53</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphoma, B-Cell - chemistry</subject><subject>Lymphoma, B-Cell - drug therapy</subject><subject>Lymphoma, B-Cell - genetics</subject><subject>Lymphoma, B-Cell - mortality</subject><subject>Lymphoma, T-Cell - chemistry</subject><subject>Lymphoma, T-Cell - drug therapy</subject><subject>Lymphoma, T-Cell - genetics</subject><subject>Lymphoma, T-Cell - mortality</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - deficiency</subject><subject>Neoplasm Proteins - physiology</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Survival Analysis</subject><subject>Treatment Failure</subject><subject>Tumor Suppressor Protein p53 - deficiency</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0M1KxDAQB_AiiuvXK0gOoqdC0jRfR11dFRbdw3ou2XS6jbZJTVrEm6_h6_kkVndF5jAD_x_DMDvJAWFMpDTjbHecsZApzmk2SQ5jfMaY5ATn-8mEYMqoyLODZLi2MQxdDyXqGEWzwZneeod0RIsApTW9D8hXaBlA9y24Hs20bYYASLsSLfyYLoJfOx9tRNahq_Q3WKZTaBr04F1658v1i3VfH58Rzd_brvatPk72Kt1EONn2o-RpdrOc3qXzx9v76eU8rTMu-1QYXoImKwIVZ5qQkijgJJdU8kxl6idigpVypTmpVAUiE0xxxZlihueE0aPkfLO3C_51gNgXrY1mvEw78EMsuBJSSc5HeLqFw6qFsuiCbXV4L_4eNYKzLdDR6KYK2hkb_52QHGM6sosNq-26frMBCjNCCAEi6GDqgo1FsGT0GwzDf6Q</recordid><startdate>19990501</startdate><enddate>19990501</enddate><creator>MØLLER, M. B</creator><creator>GERDES, A.-M</creator><creator>SKJØDT, K</creator><creator>MORTENSEN, L. S</creator><creator>PEDERSEN, N. T</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>7X8</scope></search><sort><creationdate>19990501</creationdate><title>Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma</title><author>MØLLER, M. B ; GERDES, A.-M ; SKJØDT, K ; MORTENSEN, L. S ; PEDERSEN, N. T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-7c6dea1b1ef65a11d19e61483862929ea1b575d8ba61f9fe72759696595c64153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - analysis</topic><topic>Denmark - epidemiology</topic><topic>DNA, Neoplasm - genetics</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>Genes, p53</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphoma, B-Cell - chemistry</topic><topic>Lymphoma, B-Cell - drug therapy</topic><topic>Lymphoma, B-Cell - genetics</topic><topic>Lymphoma, B-Cell - mortality</topic><topic>Lymphoma, T-Cell - chemistry</topic><topic>Lymphoma, T-Cell - drug therapy</topic><topic>Lymphoma, T-Cell - genetics</topic><topic>Lymphoma, T-Cell - mortality</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - deficiency</topic><topic>Neoplasm Proteins - physiology</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Survival Analysis</topic><topic>Treatment Failure</topic><topic>Tumor Suppressor Protein p53 - deficiency</topic><topic>Tumor Suppressor Protein p53 - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MØLLER, M. B</creatorcontrib><creatorcontrib>GERDES, A.-M</creatorcontrib><creatorcontrib>SKJØDT, K</creatorcontrib><creatorcontrib>MORTENSEN, L. S</creatorcontrib><creatorcontrib>PEDERSEN, N. T</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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MØLLER, M. B</au><au>GERDES, A.-M</au><au>SKJØDT, K</au><au>MORTENSEN, L. S</au><au>PEDERSEN, N. T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1999-05-01</date><risdate>1999</risdate><volume>5</volume><issue>5</issue><spage>1085</spage><epage>1091</epage><pages>1085-1091</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical
analysis of p53 and p21 Waf1 , a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the
basis of p53 gene mutation status and immunohistochemically detected p53 and p21 Waf1 expression in 34 lymphomas, we established an immunophenotype (Δp53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry
and was correlated with clinical parameters. Δp53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that Δp53 was
independently associated with treatment failure (relative risk, 3.8; P = 0.001). Δp53 predicted poor survival when analyzing all patients ( P = 0.0001), as well as B-cell ( P = 0.04) and T-cell NHL ( P = 0.000002). In multivariate analysis, Δp53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of Δp53 was highly significant in the low-intermediate-risk
group ( P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 Δp53 patients died within
1 year, whereas the median survival of the 28 non-Δp53 patients was 36 months. These results suggest that immunohistochemically
assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>10353742</pmid><tpages>7</tpages></addata></record> |
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| ispartof | Clinical cancer research, 1999-05, Vol.5 (5), p.1085-1091 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Apoptosis Biological and medical sciences Cyclin-Dependent Kinase Inhibitor p21 Cyclins - analysis Denmark - epidemiology DNA, Neoplasm - genetics Exons - genetics Female Genes, p53 Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphoma, B-Cell - chemistry Lymphoma, B-Cell - drug therapy Lymphoma, B-Cell - genetics Lymphoma, B-Cell - mortality Lymphoma, T-Cell - chemistry Lymphoma, T-Cell - drug therapy Lymphoma, T-Cell - genetics Lymphoma, T-Cell - mortality Male Medical sciences Middle Aged Neoplasm Proteins - deficiency Neoplasm Proteins - physiology Phenotype Prognosis Retrospective Studies Survival Analysis Treatment Failure Tumor Suppressor Protein p53 - deficiency Tumor Suppressor Protein p53 - physiology |
| title | Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma |
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