MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Australian ovarian cancer study group

doi:10.1016/j.mayocp.2017.10.023

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Australian ovarian cancer study group

Bar-Ilan University - Azrieli Faculty of Medicine

Mayo Clinic Rochester, MN
University of Calgary
Catholic University of Health and Allied Sciences
University of Tübingen
University of Melbourne
Pomeranian Medical University in Szczecin
Universidade de São Paulo
Heidelberg University
Icahn School of Medicine at Mount Sinai
The University of Sydney
Western Sydney University
Hospital de La Santa Creu I Sant Pau
Centro Nacional de Investigaciones Oncológicas
Hospital Universitario 12 de Octubre
Cedars-Sinai Medical Center
University of Texas Health Science Center at Houston
University of Pittsburgh
Stanford University
University of Cambridge
Kunming Medical College
Westmead Hospital
German Cancer Research Center
Queensland Institute of Medical Research
Cambridge University Hospitals NHS Foundation Trust
Danish Cancer Society
University of New South Wales
University of Hawai'i at Mānoa
Complejo Hospitalario Universitario de Albacete
Peter Maccallum Cancer Centre
Fundación Jiménez Díaz
Garvan Institute of Medical Research
Royal Alexandra Hospital, Edmonton
Roswell Park Cancer Institute
University College London
Alberta Health Services
University of Copenhagen
Medical University of South Carolina
University of British Columbia
Provincial Health Services Authority
Centro de Investigación Biomédica en Red
University of California at Los Angeles
Friedrich-Alexander University Erlangen-Nürnberg
Nottingham University Hospitals NHS Trust
University of Hamburg
Cancer Research UK Cambridge Institute
Cambridge Experimental Cancer Medicine Centre

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	307-320
Number of pages	14
Journal	Mayo Clinic Proceedings
Volume	93
Issue number	3
DOIs	https://doi.org/10.1016/j.mayocp.2017.10.023
State	Published - 1 Mar 2018

Bibliographical note

Publisher Copyright:
© 2017 Mayo Foundation for Medical Education and Research

Funding

Grant Support: The work was supported by grant MOP-86727 from the Canadian Institutes for Health Research; grant 478416/2009-1 from the Brazilian National Council for Scientific and Technological Development; grant RS10-533 from the Calgary Laboratory Services Internal Research Competition; grant 01 GB 9401 from the German Federal Ministry of Education and Research of Germany; grants from the German Cancer Research Center (Deutsches Krebsforschungszentrum); grants K07-CA80668, P50-CA159981, and R01CA095023 from the US National Cancer Institute; grant MO1-RR000056 from the National Institutes of Health (NIH)/National Center for Research Resources/General Clinical Research Center; grant DAMD17-02-1-0669 from the US Army Medical Research and Materiel Command; grants R01-CA122443, P50-CA136393, P30-CA15083, U01-CA71966, U01-CA69417, R01-CA16056, and K07-CA143047 from the NIH; grants C490/A10119, C490/A10123, and C490/A16561 from Cancer Research UK; grants from the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge and at University College Hospital “Womens Health Theme”; grant SFB 685 from the NIH; grants from the Eve Appeal; grants from the Oak Foundation; grants from Deutsche Forschungsgemein-schaft; grant DAMD17-01-1-0729 (A.O.C.S.) from the US Army Medical Research and Material Command; grants from the Cancer Council Victoria; grants from Queensland Cancer Fund; grants from the Cancer Council New South Wales; grants from the Cancer Council South Australia; grants from the Cancer Foundation of Western Australia; grants from the Cancer Council Tasmania; grants ID400413 and ID400281 from the National Health and Medical Research Council of Australia; grants from the Peter MacCallum Cancer Foundation and Ovarian Cancer Australia (A.O.C.S); enabling grants ID 310670 and ID 628903 (the Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group) from the National Health and Medical Research Council; grants 12/RIG/1-17 and 15/RIG/1-16 from the Cancer Institute NSW (the Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group); research grant R01- CA61107 (Malignant Ovarian Cancer Study) from the National Cancer Institute, Bethesda, MD; research grant 94 222 52 (MALOVA) from the Danish Cancer Society, Copenhagen, Denmark, and a grant (Malignant Ovarian Cancer Study) from the Mermaid I project; grant 15/TRC/1-01 (A.F. and P.R.H.) from the Cancer Institute NSW; grant SIOP-06-258-01-COUN (B.Y.K.) from the American Cancer Society Early Detection Professorship; and grant UL1TR000124 from the National Center for Advancing Translational Sciences (B.Y.K.).

Funders	Funder number
National Institutes of Health	U01-CA69417, R01-CA122443, P30-CA15083, U01-CA71966, R01-CA16056, P50-CA136393, K07-CA143047
National Cancer Institute	K07-CA80668, R01CA160565, P50-CA159981, R01CA095023
National Center for Research Resources	MO1-RR000056
Medical Research and Materiel Command	DAMD17-02-1-0669
Calgary Laboratory Services	RS10-533
Deutsches Krebsforschungszentrum
Canadian Institutes of Health Research	MOP-86727
Bundesministerium für Bildung und Forschung	01 GB 9401
Conselho Nacional de Desenvolvimento Científico e Tecnológico	478416/2009-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1016/j.mayocp.2017.10.023

Cite this

@article{dc8b095c8a66471287a46e4fc4c3e454,

title = "MyD88 and TLR4 Expression in Epithelial Ovarian Cancer",

abstract = "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.",

author = "\{Australian ovarian cancer study group\} and Block, \{Matthew S.\} and Vierkant, \{Robert A.\} and Rambau, \{Peter F.\} and Winham, \{Stacey J.\} and Philipp Wagner and Nadia Traficante and Aleksandra Toloczko and Tiezzi, \{Daniel G.\} and Taran, \{Florin Andrei\} and Peter Sinn and Weiva Sieh and Raghwa Sharma and Rothstein, \{Joseph H.\} and \{Ram{\'o}n y Cajal\}, Teresa and Luis Paz-Ares and Oleg Oszurek and Sandra Orsulic and Ness, \{Roberta B.\} and Gregg Nelson and Francesmary Modugno and Janusz Menkiszak and Valerie McGuire and McCauley, \{Bryan M.\} and Marie Mack and Jan Lubinski and Longacre, \{Teri A.\} and Zheng Li and Jenny Lester and Kennedy, \{Catherine J.\} and Kalli, \{Kimberly R.\} and Jung, \{Audrey Y.\} and Johnatty, \{Sharon E.\} and Mercedes Jimenez-Linan and Allan Jensen and Intermaggio, \{Maria P.\} and Jillian Hung and Esther Herpel and Hernandez, \{Brenda Y.\} and Hartkopf, \{Andreas D.\} and Harnett, \{Paul R.\} and Prafull Ghatage and Garc{\'i}a-Bueno, \{Jos{\'e} M.\} and Bo Gao and Sian Fereday and Ursula Eilber and Edwards, \{Robert P.\} and \{de Sousa\}, \{Christiani B.\} and \{de Andrade\}, \{Jurandyr M.\} and Anita Chudecka-Glaz and I. Haviv",

note = "Publisher Copyright: {\textcopyright} 2017 Mayo Foundation for Medical Education and Research",

year = "2018",

month = mar,

day = "1",

doi = "10.1016/j.mayocp.2017.10.023",

language = "אנגלית",

volume = "93",

pages = "307--320",

journal = "Mayo Clinic Proceedings",

issn = "0025-6196",

publisher = "Elsevier Ltd.",

number = "3",

}

TY - JOUR

T1 - MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

AU - Australian ovarian cancer study group

AU - Block, Matthew S.

AU - Vierkant, Robert A.

AU - Rambau, Peter F.

AU - Winham, Stacey J.

AU - Wagner, Philipp

AU - Traficante, Nadia

AU - Toloczko, Aleksandra

AU - Tiezzi, Daniel G.

AU - Taran, Florin Andrei

AU - Sinn, Peter

AU - Sieh, Weiva

AU - Sharma, Raghwa

AU - Rothstein, Joseph H.

AU - Ramón y Cajal, Teresa

AU - Paz-Ares, Luis

AU - Oszurek, Oleg

AU - Orsulic, Sandra

AU - Ness, Roberta B.

AU - Nelson, Gregg

AU - Modugno, Francesmary

AU - Menkiszak, Janusz

AU - McGuire, Valerie

AU - McCauley, Bryan M.

AU - Mack, Marie

AU - Lubinski, Jan

AU - Longacre, Teri A.

AU - Li, Zheng

AU - Lester, Jenny

AU - Kennedy, Catherine J.

AU - Kalli, Kimberly R.

AU - Jung, Audrey Y.

AU - Johnatty, Sharon E.

AU - Jimenez-Linan, Mercedes

AU - Jensen, Allan

AU - Intermaggio, Maria P.

AU - Hung, Jillian

AU - Herpel, Esther

AU - Hernandez, Brenda Y.

AU - Hartkopf, Andreas D.

AU - Harnett, Paul R.

AU - Ghatage, Prafull

AU - García-Bueno, José M.

AU - Gao, Bo

AU - Fereday, Sian

AU - Eilber, Ursula

AU - Edwards, Robert P.

AU - de Sousa, Christiani B.

AU - de Andrade, Jurandyr M.

AU - Chudecka-Glaz, Anita

AU - Haviv, I.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85042274578

U2 - 10.1016/j.mayocp.2017.10.023

DO - 10.1016/j.mayocp.2017.10.023

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 29502561

AN - SCOPUS:85042274578

SN - 0025-6196

VL - 93

SP - 307

EP - 320

JO - Mayo Clinic Proceedings

JF - Mayo Clinic Proceedings

IS - 3

ER -

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Abstract

Bibliographical note

Funding

UN SDGs

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