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MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Accepted version
Peer-reviewed

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Authors

Block, Matthew S 
Vierkant, Robert A 
Rambau, Peter F 
Winham, Stacey J 
Wagner, Philipp 

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.

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Keywords

Adult, Aged, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Female, Humans, Immunohistochemistry, Middle Aged, Myeloid Differentiation Factor 88, Ovarian Neoplasms, Survival Analysis, Tissue Array Analysis, Toll-Like Receptor 4

Journal Title

Mayo Clin Proc

Conference Name

Journal ISSN

0025-6196
1942-5546

Volume Title

93

Publisher

Elsevier BV
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
National Institutes of Health (NIH) (via H Lee Moffitt Cancer Center & Research Institute) (SUBAWARD # 10-15915-01-03-G2)
Cancer Research Uk (None)