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Expression of CXCR4 predicts lymph node metastasis in early breast cancer.

9525 Background: Recent experimental studies have suggested that interactions between the chemokine receptor CXCR4 and its ligand CXCL12 in host organs may play a role in breast cancer progression. There is currently no data if CXCR4 expression is associated with metastatic potential in early breast cancer. Therefore, we studied the differential expression of CXCR4 in small size lymph node positive and lymph node negative breast cancers to evaluate whether CXCR4 predicts metastasis to axillary lymph nodes.


METHODS
CXCR4 expression was evaluated on paraffin-embedded tissue sections obtained from patients with T1N0 (n=98) and T1N1 (n=99) breast cancer, using immunohistochemical staining. The intensity, staining percentage, and localization pattern (nuclear, cytoplasmic) were assessed, and positivity was categorized as follows: high cytoplasmic only versus others, and predominantly nuclear versus others. The expression patterns were correlated with lymph node status, and with other prognostic markers including ER/PR, bcl-2, HER2/neu and EGFR. Chi-square or Fisher's exact tests were used in categorical analyses.


RESULTS
High cytoplasmic only staining pattern was associated with increased lymph node metastasis (4% in T1N0 versus 13% in T1N1; p=0.04). In contrast, predominantly nuclear staining pattern was more frequently observed in lymph node negative patients (55% in T1N0 versus 36% in T1N1, p=0.008). Increased bcl-2 expression, previously reported as a good prognostic marker, was also more common in tumors that expressed predominantly nuclear CXCR4 compared to tumors with other staining patterns (74% vs 61%, respectively, p= 0.04). No significant correlation was identified between staining patterns of CXCR4, and ER/PR, HER2/neu or EGFR expression.


CONCLUSION
The different staining pattern of CXCR4 (nuclear versus cytoplasmic) appears to have different biological significance for metastatic potential of breast cancer. CXCR4 expression may be a useful marker to predict lymph node metastasis in early breast cancer. No significant financial relationships to disclose.