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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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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.
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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.

Mentions: TLR4 protein was detected by immunohistochemistry and was localized in the cytoplasm and membrane of the tumor cells (Figure1). The positive expression of TLR4 was observed in 57 cases (46.3%) of OECs. When analyzing the relationship between TLR4 expression and clinicopathological features, we found that the expression of TLR4 was not correlated with histologic grade, tumor size, mitotic count, tumor stage and tumor recurrence, but it was significantly correlated with histologic type. MyD88 was expressed in the cytoplasm of the tumor cells and the positive expression of MyD88 was observed in 45 cases (36.6%) of OECs, and it had a significant correlation with tumor stage, tumor recurrence and histologic type. NF-κB expression was recognized through cytoplasmic and/or nuclear staining of the tumor cells and was observed in 80 cases (60%) of OECs. No correlation between NF-κB expression and clinicopathological features was observed, except for histologic type. TLR4, MyD88, and NF-κB expressions were significantly higher in clear cell type of OECs than in the other histologic types of OECs (Table2).


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)

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

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

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.
Mentions: TLR4 protein was detected by immunohistochemistry and was localized in the cytoplasm and membrane of the tumor cells (Figure1). The positive expression of TLR4 was observed in 57 cases (46.3%) of OECs. When analyzing the relationship between TLR4 expression and clinicopathological features, we found that the expression of TLR4 was not correlated with histologic grade, tumor size, mitotic count, tumor stage and tumor recurrence, but it was significantly correlated with histologic type. MyD88 was expressed in the cytoplasm of the tumor cells and the positive expression of MyD88 was observed in 45 cases (36.6%) of OECs, and it had a significant correlation with tumor stage, tumor recurrence and histologic type. NF-κB expression was recognized through cytoplasmic and/or nuclear staining of the tumor cells and was observed in 80 cases (60%) of OECs. No correlation between NF-κB expression and clinicopathological features was observed, except for histologic type. TLR4, MyD88, and NF-κB expressions were significantly higher in clear cell type of OECs than in the other histologic types of OECs (Table2).

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