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, Ramon Y Cajal T, 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, Jose Garcia M, Fasching P, 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 (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 93

Pages Range: 307-320

Journal Issue: 3

DOI: 10.1016/j.mayocp.2017.10.023

Abstract

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.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).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).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.

Authors with CRIS profile

Involved external institutions

Hospital de la Santa Creu i Sant Pau Spain (ES) University of Calgary Canada (CA) Mayo Clinic United States (USA) (US) University of Sydney (USYD) Australia (AU) Icahn School of Medicine at Mount Sinai United States (USA) (US) Universitätsklinikum Tübingen Germany (DE) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Staffordshire University Germany (DE) Peter MacCallum Cancer Centre Australia (AU) University of Cambridge United Kingdom (GB) University of Pittsburgh United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Addenbrooke's Hospital United Kingdom (GB) University of New South Wales (UNSW) Australia (AU) Cedars-Sinai Medical Center United States (USA) (US) Royal Alexandra Hospital (RAH) Canada (CA) Stanford University United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Texas MD Anderson Cancer Center United States (USA) (US) Medical University of South Carolina (MUSC) United States (USA) (US) The University of Melbourne Australia (AU) Danish Cancer Society Research Center Denmark (DK) Universitätsklinikum Heidelberg Germany (DE) University College London (UCL) United Kingdom (GB) University of British Columbia Canada (CA) Alberta Health Services (AHS) Canada (CA) Complejo Hospitalario Universitario de Albacete Spain (ES) University of Hawaii (U.H.) United States (USA) (US) Fundación Jiménez Díaz Spain (ES) Nottingham University Hospitals United Kingdom (GB) University of Copenhagen Denmark (DK) Roswell Park Cancer Institute United States (USA) (US)

How to cite

APA:

Block, M.S., Vierkant, R.A., Rambau, P.F., Winham, S.J., Wagner, P., Traficante, N.,... Goode, E.L. (2018). MyD88 and TLR4 Expression in Epithelial Ovarian Cancer. Mayo Clinic Proceedings, 93(3), 307-320. https://doi.org/10.1016/j.mayocp.2017.10.023

MLA:

Block, Matthew S., et al. "MyD88 and TLR4 Expression in Epithelial Ovarian Cancer." Mayo Clinic Proceedings 93.3 (2018): 307-320.

BibTeX: Download