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 - Carter, J.
AU - Goode, Ellen L.
N1 - Publisher Copyright:
© 2017 Mayo Foundation for Medical Education and Research
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.
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U2 - 10.1016/j.mayocp.2017.10.023
DO - 10.1016/j.mayocp.2017.10.023
M3 - 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 -