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

World J Surg Oncol. 2012 Sep 17:10:193. doi: 10.1186/1477-7819-10-193.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multivariate Analysis
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-kappa B / metabolism
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Single-Blind Method
  • Survival Analysis
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Burden
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4