Expression and significance of the TLR4/MyD88 signaling pathway in ovarian epithelial cancers
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WORLD JOURNAL OF SURGICAL ONCOLOGY
RESEARCH
Open Access
Expression and significance of the TLR4/MyD88 signaling pathway in ovarian epithelial cancers Ki Hyung Kim1,2, Moo Sung Jo3, Dong Soo Suh1,2, Man Soo Yoon1,2, Dong Hun Shin4,5, Jeong Hee Lee4 and Kyung Un Choi4,5*
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. Keywords: Toll-like receptor, MyD88, Ovarian epithelial cancer
Background Ovarian epithelial cancer (OEC) is the second most common and the most lethal of all gynecologic malignancies. Early detection of OEC is difficult because there is no specific screening tool and long-term survival has not been significantly prolonged although many advances have been made in the treatment of OEC. * Correspondence: [email protected] 4 Department of Pathology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 626-770, Republic of Korea 5 Department of Pathology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 626-770, Republic of Korea Full list of author information is available at the end of the article
Many investigators have tried to understand the biology of OEC and identify the mechanisms of chemoresistance, which is one of the major cause
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