Expression and significance of the TLR4/MyD88 signaling pathway in ovarian epithelial cancers

Abstract

Background: Toll-like receptors (TLR) are a family of pattern recognition receptors that constitutes a major part of the innate immune system. The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects.

Methods: To demonstrate the role of TLR4/MyD88 signaling in ovarian epithelial cancers (OECs), we examined the expression of TLR4, MyD88 and nuclear factor- κB (NF-κB) in OECs. The expression of TLR4, MyD88, and NF-κB was detected by immunohistochemistry, and the relationships between these and clinicopathologic features in 123 cases of OECs were also analyzed.

Results: The expression of TLR4, MyD88, and NF-κB in OECs was observed in 46.3% (57/123), 36.6% (45/123) and 65% (80/123) of OEC cases, respectively. The TLR4, MyD88, and NF-κB expressions were associated with the histologic type of OECs, particularly with the clear cell type of OEC. There was no significant correlation between TLR4 or NF-κB expression and histologic grade, tumor size, mitotic count, FIGO (International Federation of Gynecology and Obstetrics) stage, disease recurrence. However, there was a significant correlation between MyD88 expression and FIGO stage, disease recurrence as well as histologic type. In univariate analysis, the expression of TLR4 and MyD88, and the coexpression of TLR4/MyD88 and TLR4/MyD88/NF-κB had a significant impact on the survival of patients with OECs. Only MyD88 expression had an independent prognostic significance in multivariate analysis.

Conclusions: Our findings suggest that the TLR4/MyD88 signaling pathway is associated with the survival of patients with OECs, and that MyD88 is an independent prognostic predictor in patients with OECs. The TLR4/MyD88 signaling pathway may be a mechanism responsible for poor prognosis in patients with clear cell type of OEC.

Figure 1

OECs showed the expressions of TLR4, MyD88, and NF-κB. (A) Serous type, TLR4, (B) serous type, MyD88, (C) serous type, NF-κB, (D) mucinous carcinoma, TLR4, (E) mucinous carcinoma, MyD88, (F) mucinous carcinoma, NF-κB, (G) clear cell type, TLR4, (H) clear cell type, MyD88, (I) clear cell type, NF-κB, (J) undifferentiated type, TLR4, (K) undifferentiated type, MyD88, (L) undifferentiated type, NF-κB. OECs, Ovarian epithelial cancers.

Figure 2

The Kaplan-Meier curves revealed the correlation between the expression of TLR4, MyD88, TLR4/MyD88 and TLR4/MyD88/NF-κB, and the overall survival (A-D).