Expression, correlation, and prognostic value of TRAF2 and TRAF4 expression in malignant plural effusion cells in human breast cancer.

Abstract

TRAF2 and TRAF4, members of the tumor necrosis factor receptor- associated factor family of intracellular signal transduction proteins, are associated with breast cancer progression and metastasis. We collected malignant serous effusion cells from the patients with breast cancer (n = 46). Cell blocks prepared from plural effusions (n = 46) and primary breast cancer (n = 50), lymph node metastases (n = 50), and normal breast tissue specimens (n = 30). The immunohistochemistry was performed for the detection of TRAF2 and TRAF4 expression with the correlation of their expression with clinicopathological parameters and survival rate analyzed. Compared with normal breast tissues, TRAF2 expression was upregulated, and nuclear TRAF4 expression was downregulated in malignant pleural effusion cells, primary tumors, and lymph node metastases (P < 0.05). Multivariate analysis revealed TRAF2 expression in pleural effusions was associated with the molecular/pathological type, venous invasion, and lymph node metastasis, while nuclear TRAF4 expression was associated with age, tumor size, venous invasion, and lymph node metastasis, clinical staging, molecular/pathological subtype and p53 status (P < 0.05). There was a significant positive correlation between TRAF2 and TRAF4 expression levels in malignant pleural effusion cells (r = 0.937; P < 0.01). Kaplan-Meire analysis demonstrated a close correlation of TRAF2 and TRAF4 expression in malignant pleural effusion cells with cumulative overall survival (P < 0.05). TRAF2 and nuclear TRAF4 expression in malignant pleural effusion cells may represent potential prognostic factors and biomarkers of invasion and metastasis in breast cancer.