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

Kim KH, Jo MS, Suh DS, Yoon MS, Shin DH, Lee JH, Choi KU - World J Surg Oncol (2012)

Bottom Line: The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects.However, there was a significant correlation between MyD88 expression and FIGO stage, disease recurrence as well as histologic type.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea.

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.

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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).
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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).

Mentions: We assessed the impact of expression of TLR4, MyD88 and NF-κB on patient survival. The mean survival of patients with expression of TLR4 in tumor tissues was 88.3 months, and it was 113.1 months in those with negative expression of TLR4, Kaplan-Meier analysis showed that there was a significant difference in the mean survival of patients with expression of TLR4 in tumor tissues and in those with negative expression of TLR4 (P = 0.030) (Figure2A). Patients with positive MyD88 expression had a worse OS than those with negative MyD88 expression (65.2 months versus 121.1 months) (P = 0.000) (Figure2B). Similar results were also found between co-expression of these proteins and OS (Table5 and Figure2C and 2D). In multivariate analysis, MyD88 was identified as an independent prognostic factor (Table6).


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

Kim KH, Jo MS, Suh DS, Yoon MS, Shin DH, Lee JH, Choi KU - World J Surg Oncol (2012)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539930&req=5

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).
Mentions: We assessed the impact of expression of TLR4, MyD88 and NF-κB on patient survival. The mean survival of patients with expression of TLR4 in tumor tissues was 88.3 months, and it was 113.1 months in those with negative expression of TLR4, Kaplan-Meier analysis showed that there was a significant difference in the mean survival of patients with expression of TLR4 in tumor tissues and in those with negative expression of TLR4 (P = 0.030) (Figure2A). Patients with positive MyD88 expression had a worse OS than those with negative MyD88 expression (65.2 months versus 121.1 months) (P = 0.000) (Figure2B). Similar results were also found between co-expression of these proteins and OS (Table5 and Figure2C and 2D). In multivariate analysis, MyD88 was identified as an independent prognostic factor (Table6).

Bottom Line: The TLR4/(Myeloid differentiation factor 88 (MyD88) signaling pathway has been shown to have oncogenic effects.However, there was a significant correlation between MyD88 expression and FIGO stage, disease recurrence as well as histologic type.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-770, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus