title: Tumor Invasiveness, Not Lymphangiogenesis, Is Correlated with Lymph Node Metastasis and Unfavorable Prognosis in Young Breast Cancer Patients (≤35 Years).
abstract: The morbidity rate of breast cancer is on the rise, and the age of onset appears to be trending toward a young age. Breast cancer in young women (BCYW) has a number of distinctive features that differ from breast cancer in middle-aged or elderly women (BCMEW). Lymphatic metastasis plays an important role in the spread of BCYW; however, the mechanisms of lymph node metastasis (LNM) in BCYW are not clear. This study aimed to investigate the mechanism of lymphatic metastasis in BCYW and to evaluate the relationships between lymphangiogenesis, the expression of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) expression, clinicopathological characteristics, and prognosis. Using immunohistochemistry, MMP-9, VEGF-C and the level of lymphatic microvessel density (LMVD) were analyzed in 106 cases of breast invasive ductal carcinoma and 20 cases of breast proliferative lesions. Compared with BCMEW, BCYW had higher MMP-9 expression, higher LNM, and more adverse prognoses. In BCYW, high MMP-9 expression was positively correlated with LNM and impaired survival time. However, in BCMEW, MMP-9 expression was not correlated with LNM or survival time. In addition, high VEGF-C expression was positively correlated with a high level of LMVD in both BCYW and BCMEW. Nevertheless, a high level of LMVD was not correlated with LNM or survival time in the two groups. More importantly, univariate and multivariate survival analysis showed that MMP-9 expression and LNM were independent prognostic factors in BCYW. Our present study indicates that lymphangiogenesis induced by VEGF-C is augmented in breast cancer; however, a higher level of lymphangiogenesis has no significant impact on LNM or survival time. We suggest that tumor invasiveness, rather than lymphangiogenesis, plays an important role in LNM among BCYW. Moreover, MMP-9 and LNM were independent prognostic factors for BCYW.
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.|Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Affiliated Hospital of Binzhou Medical University, Binzhou, China.
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Han
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.|Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Nian
authors.affiliation: Department of Vascular and Endovascular Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Nursing care and intervention, Community Health Service Center of North Binzhou, Binzhou, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Cui
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.|Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xing-Yong
authors.initials: XY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C119248:LYVE1 protein, human; D042582:Vascular Endothelial Growth Factor C; D033921:Vesicular Transport Proteins; D020780:Matrix Metalloproteinase 9