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Absence of multiple atypical chemokine binders (ACBs) and the presence of VEGF and MMP-9 predict axillary lymph node metastasis in early breast carcinomas

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Abstract

The aim of this study was to determine the frequency of axillary lymph node (ALN) metastasis of early breast cancers by evaluating the status of DARC, D6 and CCX-CKR and the levels of VEGF and MMP-9. The status of DARC, D6 and CCX-CKR and the levels VEGF and MMP-9 were evaluated in ALN– (n = 130) and ALN + (n = 88) patients with T1 breast cancer by immunohistochemical staining. For ALN, likelihood ratio χ 2-tests were used for univariate analysis and logistic regression for multivariate analysis. Univariate analysis identified the nuclear grade, VEGF and MMP-9 expression and absence of DARC, D6 and CCX-CKR as predictors of ALN involvement. When combining the three receptors (DARC, D6 and CCX-CKR) together, tumors with multiple absence (multi-absence, any two or three loss) had a higher likelihood of being ALN positive than non-multi-absence (coexpression of any two or three) tumors (56.2 vs. 27.9 %, P < 0.001). The final multivariate logistic regression revealed nuclear grade, VEGF, MMP-9 and non-multi-absence versus multi-absence to be independent predictors of ALN involvement; the odds ratio (OR) and 95 % CI for non-multi-absence tumors versus multi-absence were 0.469 (0.233–0.943). Multi-absence was also associated with the involvement of four or more lymph nodes among ALN + tumors. Moreover, tumors with multi-absence had higher VEGF (78.1 vs. 50.0 %, P < 0.001) and MMP-9 (81.3 vs. 36.1 %, P < 0.001) expression than non-multi-absence tumors. Our data highlight that the absence of DARC, D6 and CCX-CKR in combination, which is associated with higher VEGF and MMP-9 expression, predicts the presence and extent of ALN metastasis in breast cancer.

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Acknowledgments

The authors thank the studied women for their willingness to cooperate with our study. National Basic Research Program of China Grant 2006CB910501; National Natural Science Foundation of China Grants 30371580, 30570695, and 30572109; and Shanghai Science and Technology Committee Grants 03J14019, 04ZR14027, 06DJ14004, and 06DZ19504; Key Medical Project of Health Bureau of Chongqing (2012-1-125), P. R. China.

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The authors have stated that they have no conflicts interest.

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Authors and Affiliations

  1. Department of Breast Surgery, Chongqing Cancer Institute/Hospital, 181 Hanyu Road, Shapingba District, Chongqing, 400030, China

    Xiao-Hua Zeng

  2. Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, China

    Zhou-Luo Ou, Ke-Da Yu, Lan-Yun Feng, Wen-Jing Yin, Jing Li, Zhen-Zhou Shen & Zhi-Min Shao

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  1. Xiao-Hua Zeng
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Correspondence to Zhi-Min Shao.

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Xiao-Hua Zeng and Zhou-Luo Ou have contributed equally to this work.

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Zeng, XH., Ou, ZL., Yu, KD. et al. Absence of multiple atypical chemokine binders (ACBs) and the presence of VEGF and MMP-9 predict axillary lymph node metastasis in early breast carcinomas. Med Oncol 31, 145 (2014). https://doi.org/10.1007/s12032-014-0145-y

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