1. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.
- Author
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Block MS, Vierkant RA, Rambau PF, Winham SJ, Wagner P, Traficante N, Tołoczko A, Tiezzi DG, Taran FA, Sinn P, Sieh W, Sharma R, Rothstein JH, Ramón Y Cajal T, Paz-Ares L, Oszurek O, Orsulic S, Ness RB, Nelson G, Modugno F, Menkiszak J, McGuire V, McCauley BM, Mack M, Lubiński 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, García-Bueno JM, Gao B, Fereday S, Eilber U, Edwards RP, de Sousa CB, de Andrade JM, Chudecka-Głaz 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, Høgdall E, Gronwald J, Goodman MT, Gilks B, García MJ, Fasching PA, de Fazio A, Deen S, Chang-Claude J, Candido Dos Reis FJ, Campbell IG, Brenton JD, Bowtell DD, Benítez J, Pharoah PDP, Köbel M, Ramus SJ, and Goode EL
- Subjects
- Adult, Aged, Biomarkers, Tumor metabolism, Carcinoma, Ovarian Epithelial mortality, Female, Humans, Immunohistochemistry methods, Middle Aged, Ovarian Neoplasms mortality, Survival Analysis, Tissue Array Analysis methods, Carcinoma, Ovarian Epithelial metabolism, Myeloid Differentiation Factor 88 metabolism, Ovarian Neoplasms metabolism, Toll-Like Receptor 4 metabolism
- 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., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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