MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Block, MS; Vierkant, RA; Rambau, PF; Winham, SJ; Wagner, P; Traficante, N; Toloczko, A; Tiezzi, DG; Taran, FA; Sinn, P; Sieh, W; Sharma, R; Rothstein, JH; Cajal, TY; Paz-Ares, L; Oszurek, O; Orsulic, S; Ness, RB; Nelson, G; Modugno, F; Menkiszak, J; McGuire, V; McCauley, BM; Mack, M; Lubinski, J; Longacre, TA; Li, Z; Lester, J; Kennedy, CJ; Kalli, KR; Jung, AY; Johnatty, SE; Jimenez-Linan, M; Jensen, A; Intermaggio, MP; Hung, J; Herpel, E; Hernandez, BY; Hartkopf, AD; Harnett, PR; Ghatage, P; Garcia-Bueno, JM; Gao, B; Fereday, S; Eilber, U; Edwards, RP; de Sousa, CB; de Andrade, JM; Chudecka-Glaz, A; Chenevix-Trench, G; Cazorla, A; Brucker, SY; Alsop, J; Whittemore, AS; Steed, H; Staebler, A; Moysich, KB; Menon, U; Koziak, JM; Kommoss, S; Kjaer, SK; Kelemen, LE; Karlan, BY; Huntsman, DG; Hogdall, E; Gronwald, J; Goodman, MT; Gilks, B; Garcia, MJ; Fasching, PA; de Fazio, A; Deen, S; Chang-Claude, J; dos Reis, FJC; Campbell, IG; Brenton, JD; Bowtell, DD; Benitez, J; Pharoah, PDP; Kobel, M; Ramus, SJ; Goode, EL

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical stai...

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Detalhes bibliográficos
Autores:	Block, MS, Vierkant, RA, Rambau, PF, Winham, SJ, Wagner, P, Traficante, N, Toloczko, A, Tiezzi, DG, Taran, FA, Sinn, P, Sieh, W, Sharma, R, Rothstein, JH, Cajal, TY, Paz-Ares, L, Oszurek, O, Orsulic, S, Ness, RB, Nelson, G, Modugno, F, Menkiszak, J, McGuire, V, McCauley, BM, Mack, M, Lubinski, J, Longacre, TA, Li, Z, Lester, J, Kennedy, CJ, Kalli, KR, Jung, AY, Johnatty, SE, Jimenez-Linan, M, Jensen, A, Intermaggio, MP, Hung, J, Herpel, E, Hernandez, BY, Hartkopf, AD, Harnett, PR, Ghatage, P, Garcia-Bueno, JM, Gao, B, Fereday, S, Eilber, U, Edwards, RP, de Sousa, CB, de Andrade, JM, Chudecka-Glaz, A, Chenevix-Trench, G, Cazorla, A, Brucker, SY, Alsop, J, Whittemore, AS, Steed, H, Staebler, A, Moysich, KB, Menon, U, Koziak, JM, Kommoss, S, Kjaer, SK, Kelemen, LE, Karlan, BY, Huntsman, DG, Hogdall, E, Gronwald, J, Goodman, MT, Gilks, B, Garcia, MJ, Fasching, PA, de Fazio, A, Deen, S, Chang-Claude, J, dos Reis, FJC, Campbell, IG, Brenton, JD, Bowtell, DD, Benitez, J, Pharoah, PDP, Kobel, M, Ramus, SJ, Goode, EL
Tipo de documento:	artigo
Estado:	Versão publicada
Data de publicação:	2018
País:	España
Recursos:	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositório:	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:	oai:iibsantpau.fundanetsuite.com:p14068
Acesso em linha:	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14068
Access Level:	Acceso aberto

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spelling	MyD88 and TLR4 Expression in Epithelial Ovarian CancerBlock, MSVierkant, RARambau, PFWinham, SJWagner, PTraficante, NToloczko, ATiezzi, DGTaran, FASinn, PSieh, WSharma, RRothstein, JHCajal, TYPaz-Ares, LOszurek, OOrsulic, SNess, RBNelson, GModugno, FMenkiszak, JMcGuire, VMcCauley, BMMack, MLubinski, JLongacre, TALi, ZLester, JKennedy, CJKalli, KRJung, AYJohnatty, SEJimenez-Linan, MJensen, AIntermaggio, MPHung, JHerpel, EHernandez, BYHartkopf, ADHarnett, PRGhatage, PGarcia-Bueno, JMGao, BFereday, SEilber, UEdwards, RPde Sousa, CBde Andrade, JMChudecka-Glaz, AChenevix-Trench, GCazorla, ABrucker, SYAlsop, JWhittemore, ASSteed, HStaebler, AMoysich, KBMenon, UKoziak, JMKommoss, SKjaer, SKKelemen, LEKarlan, BYHuntsman, DGHogdall, EGronwald, JGoodman, MTGilks, BGarcia, MJFasching, PAde Fazio, ADeen, SChang-Claude, Jdos Reis, FJCCampbell, IGBrenton, JDBowtell, DDBenitez, JPharoah, PDPKobel, MRamus, SJGoode, ELObjective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes. (C) 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.ELSEVIER SCIENCE INC2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14068MAYO CLINIC PROCEEDINGSISSN: 00256196ISSNe: 19425546reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p140682026-06-14T12:41:47Z
dc.title.none.fl_str_mv	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
title	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
spellingShingle	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer Block, MS
title_short	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
title_full	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
title_fullStr	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
title_full_unstemmed	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
title_sort	MyD88 and TLR4 Expression in Epithelial Ovarian Cancer
dc.creator.none.fl_str_mv	Block, MS Vierkant, RA Rambau, PF Winham, SJ Wagner, P Traficante, N Toloczko, A Tiezzi, DG Taran, FA Sinn, P Sieh, W Sharma, R Rothstein, JH Cajal, TY Paz-Ares, L Oszurek, O Orsulic, S Ness, RB Nelson, G Modugno, F Menkiszak, J McGuire, V McCauley, BM Mack, M Lubinski, J Longacre, TA Li, Z Lester, J Kennedy, CJ Kalli, KR Jung, AY Johnatty, SE Jimenez-Linan, M Jensen, A Intermaggio, MP Hung, J Herpel, E Hernandez, BY Hartkopf, AD Harnett, PR Ghatage, P Garcia-Bueno, JM Gao, B Fereday, S Eilber, U Edwards, RP de Sousa, CB de Andrade, JM Chudecka-Glaz, A Chenevix-Trench, G Cazorla, A Brucker, SY Alsop, J Whittemore, AS Steed, H Staebler, A Moysich, KB Menon, U Koziak, JM Kommoss, S Kjaer, SK Kelemen, LE Karlan, BY Huntsman, DG Hogdall, E Gronwald, J Goodman, MT Gilks, B Garcia, MJ Fasching, PA de Fazio, A Deen, S Chang-Claude, J dos Reis, FJC Campbell, IG Brenton, JD Bowtell, DD Benitez, J Pharoah, PDP Kobel, M Ramus, SJ Goode, EL
author	Block, MS
author_facet	Block, MS Vierkant, RA Rambau, PF Winham, SJ Wagner, P Traficante, N Toloczko, A Tiezzi, DG Taran, FA Sinn, P Sieh, W Sharma, R Rothstein, JH Cajal, TY Paz-Ares, L Oszurek, O Orsulic, S Ness, RB Nelson, G Modugno, F Menkiszak, J McGuire, V McCauley, BM Mack, M Lubinski, J Longacre, TA Li, Z Lester, J Kennedy, CJ Kalli, KR Jung, AY Johnatty, SE Jimenez-Linan, M Jensen, A Intermaggio, MP Hung, J Herpel, E Hernandez, BY Hartkopf, AD Harnett, PR Ghatage, P Garcia-Bueno, JM Gao, B Fereday, S Eilber, U Edwards, RP de Sousa, CB de Andrade, JM Chudecka-Glaz, A Chenevix-Trench, G Cazorla, A Brucker, SY Alsop, J Whittemore, AS Steed, H Staebler, A Moysich, KB Menon, U Koziak, JM Kommoss, S Kjaer, SK Kelemen, LE Karlan, BY Huntsman, DG Hogdall, E Gronwald, J Goodman, MT Gilks, B Garcia, MJ Fasching, PA de Fazio, A Deen, S Chang-Claude, J dos Reis, FJC Campbell, IG Brenton, JD Bowtell, DD Benitez, J Pharoah, PDP Kobel, M Ramus, SJ Goode, EL
author_role	author
author2	Vierkant, RA Rambau, PF Winham, SJ Wagner, P Traficante, N Toloczko, A Tiezzi, DG Taran, FA Sinn, P Sieh, W Sharma, R Rothstein, JH Cajal, TY Paz-Ares, L Oszurek, O Orsulic, S Ness, RB Nelson, G Modugno, F Menkiszak, J McGuire, V McCauley, BM Mack, M Lubinski, J Longacre, TA Li, Z Lester, J Kennedy, CJ Kalli, KR Jung, AY Johnatty, SE Jimenez-Linan, M Jensen, A Intermaggio, MP Hung, J Herpel, E Hernandez, BY Hartkopf, AD Harnett, PR Ghatage, P Garcia-Bueno, JM Gao, B Fereday, S Eilber, U Edwards, RP de Sousa, CB de Andrade, JM Chudecka-Glaz, A Chenevix-Trench, G Cazorla, A Brucker, SY Alsop, J Whittemore, AS Steed, H Staebler, A Moysich, KB Menon, U Koziak, JM Kommoss, S Kjaer, SK Kelemen, LE Karlan, BY Huntsman, DG Hogdall, E Gronwald, J Goodman, MT Gilks, B Garcia, MJ Fasching, PA de Fazio, A Deen, S Chang-Claude, J dos Reis, FJC Campbell, IG Brenton, JD Bowtell, DD Benitez, J Pharoah, PDP Kobel, M Ramus, SJ Goode, EL
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
description	Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes. (C) 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.
publishDate	2018
dc.date.none.fl_str_mv	2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14068
url	https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14068
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	ELSEVIER SCIENCE INC
publisher.none.fl_str_mv	ELSEVIER SCIENCE INC
dc.source.none.fl_str_mv	MAYO CLINIC PROCEEDINGS ISSN: 00256196 ISSNe: 19425546 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str	Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection	r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.198674

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

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