MDR1 expression is associated with adverse survival in melanoma of the uveal tract
Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been asso...
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| Veröffentlicht in: | Human pathology 1998-06, Vol.29 (6), p.594-598 |
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| creator | Dunne, Barbara M. McNamara, Morgan Clynes, Martin Shering, Stephen G. Larkin, Anne Marie Moran, Elizabeth Barnes, Colma Kennedy, Susan M. |
| description | Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (
P = .004) between MDR1 expression by tumor cells and shorter survival times (
n = 96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors. |
| doi_str_mv | 10.1016/S0046-8177(98)80008-7 |
| format | Article |
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P = .004) between MDR1 expression by tumor cells and shorter survival times (
n = 96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/S0046-8177(98)80008-7</identifier><identifier>PMID: 9635679</identifier><identifier>CODEN: HPCQA4</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism ; Biological and medical sciences ; Child ; Drug Resistance, Multiple ; Female ; Genes, MDR ; Hematologic and hematopoietic diseases ; Humans ; Immunohistochemistry ; Ireland ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; MDR1 ; Medical sciences ; Melanoma - metabolism ; Melanoma - mortality ; Melanoma - pathology ; Middle Aged ; Proportional Hazards Models ; survival ; Survival Rate ; uveal melanoma ; Uveal Neoplasms - metabolism ; Uveal Neoplasms - mortality ; Uveal Neoplasms - pathology</subject><ispartof>Human pathology, 1998-06, Vol.29 (6), p.594-598</ispartof><rights>1998</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-4f93f7b9925c51c532e283d361711c61c43f39584e27920511a139acdf008263</citedby><cites>FETCH-LOGICAL-c389t-4f93f7b9925c51c532e283d361711c61c43f39584e27920511a139acdf008263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817798800087$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2320648$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9635679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dunne, Barbara M.</creatorcontrib><creatorcontrib>McNamara, Morgan</creatorcontrib><creatorcontrib>Clynes, Martin</creatorcontrib><creatorcontrib>Shering, Stephen G.</creatorcontrib><creatorcontrib>Larkin, Anne Marie</creatorcontrib><creatorcontrib>Moran, Elizabeth</creatorcontrib><creatorcontrib>Barnes, Colma</creatorcontrib><creatorcontrib>Kennedy, Susan M.</creatorcontrib><title>MDR1 expression is associated with adverse survival in melanoma of the uveal tract</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (
P = .004) between MDR1 expression by tumor cells and shorter survival times (
n = 96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Drug Resistance, Multiple</subject><subject>Female</subject><subject>Genes, MDR</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Ireland</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>MDR1</subject><subject>Medical sciences</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - mortality</subject><subject>Melanoma - pathology</subject><subject>Middle Aged</subject><subject>Proportional Hazards Models</subject><subject>survival</subject><subject>Survival Rate</subject><subject>uveal melanoma</subject><subject>Uveal Neoplasms - metabolism</subject><subject>Uveal Neoplasms - mortality</subject><subject>Uveal Neoplasms - pathology</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EKtvCT6jkA0L0kNZjx7F9QlX5lIoqld4t15moRvlYPEko_x63u9orpzm8z3heP4ydgjgHAc3FTyHqprJgzAdnz6wQwlbmBduAVrKyysmXbHNAXrNjol9CAOhaH7Ej1yjdGLdhtz8-3QLHx21GojSNPBEPRFNMYcaW_0nzAw_tipmQ05LXtIaep5EP2IdxGgKfOj4_IF9WLMGcQ5zfsFdd6Anf7ucJu_vy-e7qW3V98_X71eV1FZV1c1V3TnXm3jmpo4ZYWqO0qlUNGIDYQKxVp5y2NUrjpNAAAZQLse3KT2WjTtj73bPbPP1ekGY_JIrYl144LeSNc1paqQuod2DME1HGzm9zGkL-60H4J5X-WaV_8uSd9c8qvSl7p_sDy_2A7WFr767k7_Z5oBj6LocxJjpgUknR1LZgH3cYFhdrwuwpJhwjtiljnH07pf8U-QcJho6a</recordid><startdate>19980601</startdate><enddate>19980601</enddate><creator>Dunne, Barbara M.</creator><creator>McNamara, Morgan</creator><creator>Clynes, Martin</creator><creator>Shering, Stephen G.</creator><creator>Larkin, Anne Marie</creator><creator>Moran, Elizabeth</creator><creator>Barnes, Colma</creator><creator>Kennedy, Susan M.</creator><general>Elsevier Inc</general><general>Elsevier</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></search><sort><creationdate>19980601</creationdate><title>MDR1 expression is associated with adverse survival in melanoma of the uveal tract</title><author>Dunne, Barbara M. ; McNamara, Morgan ; Clynes, Martin ; Shering, Stephen G. ; Larkin, Anne Marie ; Moran, Elizabeth ; Barnes, Colma ; Kennedy, Susan M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-4f93f7b9925c51c532e283d361711c61c43f39584e27920511a139acdf008263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Drug Resistance, Multiple</topic><topic>Female</topic><topic>Genes, MDR</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Ireland</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>MDR1</topic><topic>Medical sciences</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - mortality</topic><topic>Melanoma - pathology</topic><topic>Middle Aged</topic><topic>Proportional Hazards Models</topic><topic>survival</topic><topic>Survival Rate</topic><topic>uveal melanoma</topic><topic>Uveal Neoplasms - metabolism</topic><topic>Uveal Neoplasms - mortality</topic><topic>Uveal Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dunne, Barbara M.</creatorcontrib><creatorcontrib>McNamara, Morgan</creatorcontrib><creatorcontrib>Clynes, Martin</creatorcontrib><creatorcontrib>Shering, Stephen G.</creatorcontrib><creatorcontrib>Larkin, Anne Marie</creatorcontrib><creatorcontrib>Moran, Elizabeth</creatorcontrib><creatorcontrib>Barnes, Colma</creatorcontrib><creatorcontrib>Kennedy, Susan M.</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><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dunne, Barbara M.</au><au>McNamara, Morgan</au><au>Clynes, Martin</au><au>Shering, Stephen G.</au><au>Larkin, Anne Marie</au><au>Moran, Elizabeth</au><au>Barnes, Colma</au><au>Kennedy, Susan M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MDR1 expression is associated with adverse survival in melanoma of the uveal tract</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>1998-06-01</date><risdate>1998</risdate><volume>29</volume><issue>6</issue><spage>594</spage><epage>598</epage><pages>594-598</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>Metastatic uveal melanoma is profoundly chemoresistant and has a very poor outcome. We have previously shown that the MDR1 gene and its gene product P-glycoprotein (P-gp), which are known to cause drug resistance in cancer cells, are expressed in ocular melanoma. Overexpression of MDR1 has been associated with a poor survival in some tumor types treated by chemotherapy and in some untreated tumours. To assess whether MDR1 expression is of prognostic value in uveal melanoma, we evaluated the expression of MDR1 by immunohistochemistry in 108 cases. Three semiquantitative grades were used to evaluate positive staining. We detected MDR1 expression in 80% of cases; 28% showed grade I staining; 30%, grade II staining; and 22%, grade III staining. There was a statistically significant association (
P = .004) between MDR1 expression by tumor cells and shorter survival times (
n = 96), which was most striking at grade III levels of expression. Multivariate analysis showed that MDR1 expression is an independent prognostic indicator of poor survival. We conclude that (1) MDR1 may be involved in chemoresistance and tumor propagation in primary uveal melanoma, and (2) increasing levels of expression are prognostically significant and may prove a useful marker of tumor invasiveness, independent of established prognostic factors.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9635679</pmid><doi>10.1016/S0046-8177(98)80008-7</doi><tpages>5</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism Biological and medical sciences Child Drug Resistance, Multiple Female Genes, MDR Hematologic and hematopoietic diseases Humans Immunohistochemistry Ireland Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male MDR1 Medical sciences Melanoma - metabolism Melanoma - mortality Melanoma - pathology Middle Aged Proportional Hazards Models survival Survival Rate uveal melanoma Uveal Neoplasms - metabolism Uveal Neoplasms - mortality Uveal Neoplasms - pathology |
| title | MDR1 expression is associated with adverse survival in melanoma of the uveal tract |
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