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

Background: 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.

Methods: 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.

Results: 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).

Conclusion: TRAF2 and nuclear TRAF4 expression in malignant pleural effusion cells may represent potential prognostic factors and biomarkers of invasion and metastasis in breast cancer.