Expression of pigment epithelium-derived factor is associated with a good prognosis and is correlated with epithelial-mesenchymal transition-related genes in infiltrating ductal breast carcinoma

Abstract

Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E-cadherin, vimentin, Snail and nuclear factor-κB (NF-κB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-κB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-κB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF- and E-cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF-κB-positive tumors. Vimentin, E-cadherin and NF-κB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation.

Keywords: breast cancer; epithelial-mesenchymal transition; pigment epithelium-derived factor; prognosis.

Figure 1.

Immunohistochemical analysis of E-cadherin, vimentin, Snail and NF-κB in invasive ductal breast cancer (IDC) and normal breast samples (original magnification, ×400). (A) Immunostaining of pigment epithelium-derived factor (PEDF) mainly in the cytoplasm of certain epithelial cells (yellow-brown granules indicated by the red arrow). (B)Immunostaining of E-cadherin in the cell membranes of normal breast tissues (yellow-brown granules indicated by the red arrow). (C) Immunostaining of vimentin in the normal breast tissues. (D) Immunostaining of nuclear factor κβ (NF-κβ) in the normal breast tissues. (E) Immunostaining of Snail in the normal breast tissues. (F) Immunostaining of PEDF in invasive ductal breast cancer samples. (G) Immunostaining of E-cadherin in invasive ductal breast cancer samples. (H) Immunostaining of vimentin in the cytoplasm of certain epithelial cells (yellow-brown granules indicated by the red arrow). (I) Immunostaining of NF-κβ in the nuclei and cytoplasm of cancer cells in a positive specimen (yellow-brown granules indicated by a red arrow). (J) Immunostaining of Snail in the cytoplasm of IDC cells in a positive specimen (yellow-brown granules indicated by a red arrow).

Figure 2.

Kaplan-Meier analysis for overall survival curves of breast cancer patients with pigment epithelium-derived factor (PEDF), E-cadherin, vimentin, Snail and nuclear factor κB (NF-κB) expression. Survival curves are stratified by negative (−) and positive (+) (A) PEDF, (B) E-cadherin, (C) vimentin, (D) Snail and (E) NF-κB expression.

Figure 3.

Kaplan-Meier analysis for disease-free survival curves of breast cancer patients with pigment epithelium-derived factor (PEDF), E-cadherin, vimentin, Snail and nuclear factor κB (NF-κB) expression. Survival curves are stratified by negative (−) and positive (+) (A) PEDF, (B) E-cadherin, (C) vimentin, (D) Snail and (E) NF-κB expression.