title: Absence of multiple atypical chemokine binders (ACBs) and the presence of VEGF and MMP-9 predict axillary lymph node metastasis in early breast carcinomas.
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.
authors.affiliation: Department of Breast Surgery, Chongqing Cancer Institute/Hospital, 181 Hanyu Road, Shapingba District, Chongqing, 400030, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zeng
authors.forename: Zhou-Luo
authors.initials: ZL
authors.lastname: Ou
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.forename: Lan-Yun
authors.initials: LY
authors.lastname: Feng
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D016009:Chi-Square Distribution; D004375:Duffy Blood-Group System / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D016017:Odds Ratio; D054388:Receptors, CCR / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*
chemical_list: C473745:ACKR1 protein, human; C408223:ACKR4 protein, human; D004375:Duffy Blood-Group System; D054388:Receptors, CCR; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9
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