MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Australian Ovarian Cancer Study Group, Matthew S. Block, Robert A. Vierkant, Peter F. Rambau, Stacey J. Winham, Philipp Wagner, Nadia Traficante, Aleksandra Toloczko, Daniel G. Tiezzi, Florin Andrei Taran, Peter Sinn, Weiva Sieh, Raghwa Sharma, Joseph H. Rothstein, Teresa Ramón y Cajal, Luis Paz-Ares, Oleg Oszurek, Sandra Orsulic, Roberta B. Ness, Gregg NelsonFrancesmary Modugno, Janusz Menkiszak, Valerie McGuire, Bryan M. McCauley, Marie Mack, Jan Lubinski, Teri A. Longacre, Zheng Li, Jenny Lester, Catherine J. Kennedy, Kimberly R. Kalli, Audrey Y. Jung, Sharon E. Johnatty, Mercedes Jimenez-Linan, Allan Jensen, Maria P. Intermaggio, Jillian Hung, Esther Herpel, Brenda Y. Hernandez, Andreas D. Hartkopf, Paul R. Harnett, Prafull Ghatage, José M. García-Bueno, Bo Gao, Sian Fereday, Ursula Eilber, Robert P. Edwards, Christiani B. de Sousa, Jurandyr M. de Andrade, Anita Chudecka-Glaz, Georgia Chenevix-Trench, Alicia Cazorla, Sara Y. Brucker, David D. Bowtell, S. Brown, M. Links, J. Hill, B. Brown

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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). 


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.

Original languageEnglish
Pages (from-to)307-320
Number of pages14
JournalMayo Clinic Proceedings
Issue number3
Publication statusPublished - 1 Mar 2018


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