Cytoplasmic CXCR4 High-Expression Exhibits Distinct Poor Clinicopathological Characteristics and Predicts Poor Prognosis in Triple-Negative Breast Cancer

H.-W.      Chen; C.-W.      Du; X.-L.      Wei; U.-S.      Khoo; G.-J.      Zhang

Abstract

CXC chemokine receptor type 4 (CXCR4) plays a prominent role in cancer progression and metastasis. However, its association with breast cancer subtypes is still unknown. In the current study, we analyzed the expression level and the cellular location of CXCR4 in 175 cases of human breast tumors, including 75 cases of triple-negative breast cancers (TNBCs), 41 cases of luminal-subtypes and 60 cases of HER2-positive breast cancers by using immmunohistochemistry (IHC). We found that CXCR4 was expressed more frequently in the TNBCs than in other subtypes (71% for TNBC vs 44% for HER2-positive and 37% for luminal subtype, p<0.001). In the TNBC group, CXCR4 positive patients have a significantly higher rate of visceral metastasis (liver, lung and brain). The expression level of CXCR4 is also significantly related to tumor size, advanced TNM stage, shorter overall- and disease-free survival. However, in luminal or HER2-positive breast cancer groups, CXCR4 is not correlated with such clinico-pathological characteristics and survival. Taken together, our data indicate that CXCR4 might exert its function exclusively in TNBC patients, suggesting that targeting CXCR4 might be an effective therapy for TNBC patients.

Keywords: Chemokine (C-X-C motif) ligand 12 (CXCL12), CXC chemokine receptor types 4 (CXCR4), HER2-neu, HER2-positive breast cancer, luminal breast cancer, triple negative breast cancer, visceral organ specific metastases

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