Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients

Background: Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosin...

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Veröffentlicht in:British journal of cancer 2013-04, Vol.108 (8), p.1641-1647
Hauptverfasser: El Hajj, P, Journe, F, Wiedig, M, Laios, I, Salès, F, Galibert, M-D, Van Kempen, L C, Spatz, A, Badran, B, Larsimont, D, Awada, A, Ghanem, G
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container_issue 8
container_start_page 1641
container_title British journal of cancer
container_volume 108
creator El Hajj, P
Journe, F
Wiedig, M
Laios, I
Salès, F
Galibert, M-D
Van Kempen, L C
Spatz, A
Badran, B
Larsimont, D
Awada, A
Ghanem, G
description Background: Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P =0.005 and 0.01, respectively), increased Breslow thickness (Spearman’s rho test, P
doi_str_mv 10.1038/bjc.2013.115
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Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P =0.005 and 0.01, respectively), increased Breslow thickness (Spearman’s rho test, P &lt;0.001) and the presence of ulceration (Mann–Whitney test, P =0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P -value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups. Conclusion: High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2013.115</identifier><identifier>PMID: 23519055</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/1620/1616 ; 631/67/322 ; 692/53/2422 ; 692/699/67/1813/1634 ; Adolescent ; Adult ; Aged ; Biological and medical sciences ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Disease-Free Survival ; Drug Resistance ; Epidemiology ; Female ; Genetics ; Hematologic and hematopoietic diseases ; Humans ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Life Sciences ; Lymph Nodes - metabolism ; Lymph Nodes - pathology ; Lymphatic Metastasis ; Lymphatic system ; Male ; Medical prognosis ; Medical research ; Medical sciences ; Melanoma ; Melanoma - enzymology ; Melanoma - genetics ; Melanoma - pathology ; Membrane Glycoproteins - biosynthesis ; Membrane Glycoproteins - genetics ; Metastasis ; Middle Aged ; Molecular Diagnostics ; Molecular Medicine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Nerve Growth Factors - biosynthesis ; Nerve Growth Factors - genetics ; Oncology ; Oxidoreductases - biosynthesis ; Oxidoreductases - genetics ; Pathology ; Proteins ; Real-Time Polymerase Chain Reaction ; Risk Factors ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins - biosynthesis ; S100 Proteins - genetics ; Skin cancer ; Survival Rate ; Tumors ; Young Adult</subject><ispartof>British journal of cancer, 2013-04, Vol.108 (8), p.1641-1647</ispartof><rights>The Author(s) 2013</rights><rights>2014 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Apr 30, 2013</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2013 Cancer Research UK 2013 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c547t-b8a928fba0cd62b0f53b2a6de86230c21366fcec262fd2fc46eb642166d3d3f23</citedby><cites>FETCH-LOGICAL-c547t-b8a928fba0cd62b0f53b2a6de86230c21366fcec262fd2fc46eb642166d3d3f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668475/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668475/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=27302485$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23519055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01064483$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>El Hajj, P</creatorcontrib><creatorcontrib>Journe, F</creatorcontrib><creatorcontrib>Wiedig, M</creatorcontrib><creatorcontrib>Laios, I</creatorcontrib><creatorcontrib>Salès, F</creatorcontrib><creatorcontrib>Galibert, M-D</creatorcontrib><creatorcontrib>Van Kempen, L C</creatorcontrib><creatorcontrib>Spatz, A</creatorcontrib><creatorcontrib>Badran, B</creatorcontrib><creatorcontrib>Larsimont, D</creatorcontrib><creatorcontrib>Awada, A</creatorcontrib><creatorcontrib>Ghanem, G</creatorcontrib><title>Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background: Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P =0.005 and 0.01, respectively), increased Breslow thickness (Spearman’s rho test, P &lt;0.001) and the presence of ulceration (Mann–Whitney test, P =0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P -value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups. Conclusion: High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.</description><subject>631/250/1620/1616</subject><subject>631/67/322</subject><subject>692/53/2422</subject><subject>692/699/67/1813/1634</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genetics</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Life Sciences</subject><subject>Lymph Nodes - metabolism</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic Metastasis</subject><subject>Lymphatic system</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Melanoma - enzymology</subject><subject>Melanoma - genetics</subject><subject>Melanoma - pathology</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Nerve Growth Factors - biosynthesis</subject><subject>Nerve Growth Factors - genetics</subject><subject>Oncology</subject><subject>Oxidoreductases - biosynthesis</subject><subject>Oxidoreductases - genetics</subject><subject>Pathology</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Risk Factors</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>S100 Calcium Binding Protein beta Subunit</subject><subject>S100 Proteins - biosynthesis</subject><subject>S100 Proteins - genetics</subject><subject>Skin cancer</subject><subject>Survival Rate</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkt-L1DAQx4so3nr65rMERFCwa340afdFWA71hEVBzueQptNt1rbpJe3ivvi3O3XX8zx8EAIhmc_MdzL5JslTRpeMiuJNubNLTplYMibvJQsmBU9ZwfP7yYJSmqd0xelZ8ijGHR5XtMgfJmdcSLaiUi6SH1eH4KPrTYQ0QGtGqMgQ_AiuJ4x0Xz6tCXwfAsTofE_wsj10Q0N6XwHpYDQRF0RMgcrZMRK_h2DalsQp7N3etHNK47ZNGlz8hhmt6X1nyGBGB_0YHycPatNGeHLaz5Ov799dXVymm88fPl6sN6mVWT6mZWFWvKhLQ22leElrKUpuVAWF4oJazoRStQXLFa8rXttMQakyzpSqRCVqLs6Tt8e6w1R2UFnUxjb1EFxnwkF74_Tfkd41euv3GgsXWS6xwKtjgeZO2uV6o-c7yqjKskLsGbIvT2LBX08QR925aKHFt4OfosZu86yQUsn_QLM8L_JczujzO-jOT6HHqf2iBFpAztqvj5TFb40B6ptmGdWzXzT6Rc9-0egXxJ_dnssN_NsgCLw4ASZa09bB9NbFPxzqcnwLcumRixjqtxBudfcv4Z_JItjT</recordid><startdate>20130430</startdate><enddate>20130430</enddate><creator>El Hajj, P</creator><creator>Journe, F</creator><creator>Wiedig, M</creator><creator>Laios, I</creator><creator>Salès, F</creator><creator>Galibert, M-D</creator><creator>Van Kempen, L C</creator><creator>Spatz, A</creator><creator>Badran, B</creator><creator>Larsimont, D</creator><creator>Awada, A</creator><creator>Ghanem, G</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Cancer Research UK</general><scope>C6C</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</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>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TM</scope><scope>1XC</scope><scope>5PM</scope></search><sort><creationdate>20130430</creationdate><title>Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients</title><author>El Hajj, P ; Journe, F ; Wiedig, M ; Laios, I ; Salès, F ; Galibert, M-D ; Van Kempen, L C ; Spatz, A ; Badran, B ; Larsimont, D ; Awada, A ; Ghanem, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c547t-b8a928fba0cd62b0f53b2a6de86230c21366fcec262fd2fc46eb642166d3d3f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/250/1620/1616</topic><topic>631/67/322</topic><topic>692/53/2422</topic><topic>692/699/67/1813/1634</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Genetics</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Life Sciences</topic><topic>Lymph Nodes - metabolism</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic Metastasis</topic><topic>Lymphatic system</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Melanoma</topic><topic>Melanoma - enzymology</topic><topic>Melanoma - genetics</topic><topic>Melanoma - pathology</topic><topic>Membrane Glycoproteins - biosynthesis</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Nerve Growth Factors - biosynthesis</topic><topic>Nerve Growth Factors - genetics</topic><topic>Oncology</topic><topic>Oxidoreductases - biosynthesis</topic><topic>Oxidoreductases - genetics</topic><topic>Pathology</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Risk Factors</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>S100 Calcium Binding Protein beta Subunit</topic><topic>S100 Proteins - biosynthesis</topic><topic>S100 Proteins - genetics</topic><topic>Skin cancer</topic><topic>Survival Rate</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Hajj, P</creatorcontrib><creatorcontrib>Journe, F</creatorcontrib><creatorcontrib>Wiedig, M</creatorcontrib><creatorcontrib>Laios, I</creatorcontrib><creatorcontrib>Salès, F</creatorcontrib><creatorcontrib>Galibert, M-D</creatorcontrib><creatorcontrib>Van Kempen, L C</creatorcontrib><creatorcontrib>Spatz, A</creatorcontrib><creatorcontrib>Badran, B</creatorcontrib><creatorcontrib>Larsimont, D</creatorcontrib><creatorcontrib>Awada, A</creatorcontrib><creatorcontrib>Ghanem, G</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P =0.005 and 0.01, respectively), increased Breslow thickness (Spearman’s rho test, P &lt;0.001) and the presence of ulceration (Mann–Whitney test, P =0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P -value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups. Conclusion: High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23519055</pmid><doi>10.1038/bjc.2013.115</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/250/1620/1616
631/67/322
692/53/2422
692/699/67/1813/1634
Adolescent
Adult
Aged
Biological and medical sciences
Biomarkers, Tumor - biosynthesis
Biomarkers, Tumor - genetics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Disease-Free Survival
Drug Resistance
Epidemiology
Female
Genetics
Hematologic and hematopoietic diseases
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Life Sciences
Lymph Nodes - metabolism
Lymph Nodes - pathology
Lymphatic Metastasis
Lymphatic system
Male
Medical prognosis
Medical research
Medical sciences
Melanoma
Melanoma - enzymology
Melanoma - genetics
Melanoma - pathology
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - genetics
Metastasis
Middle Aged
Molecular Diagnostics
Molecular Medicine
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Nerve Growth Factors - biosynthesis
Nerve Growth Factors - genetics
Oncology
Oxidoreductases - biosynthesis
Oxidoreductases - genetics
Pathology
Proteins
Real-Time Polymerase Chain Reaction
Risk Factors
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
S100 Calcium Binding Protein beta Subunit
S100 Proteins - biosynthesis
S100 Proteins - genetics
Skin cancer
Survival Rate
Tumors
Young Adult
title Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients
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