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.

The Effect of Breast Parenchymal Density on Breast Cancer Subtypes and Prognostic Factors

“…LVI is thought to mediate cancer dissemination, 39,40 and is accompanied by poor prognosis and pathological characteristics. 41,42 In our study, lymphovascular invasion positivity was found to be increased with increased density (p=0.002). Due to our short follow-up period, we could not evaluate the effect of lymphovascular invasion positivity on prognosis.…”

Lymphovascular invasion is an independent predictor of survival in breast cancer after neoadjuvant chemotherapy

“…Lymphangiogenesis is thought to correlate with lymph node metastasis and may be driven by factors secreted by tumor cells and their environment such as vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 9 (MMP-9). [35-37] Studies also show that lymphangiogenesis is affected by histology subtype, with TNBC patients having higher densities of lymphatic microvessels and VEGF-C compared with non-TNBC patients, and subsequently worse OS. [38,20,39] The underlying mechanism for LVI as an independent predictor of poor PFS appears independent from existing nodal invasion, and as it appears to vary with subtype, may reflect not only the aggressiveness of the underlying tumor but also the surrounding tumor micro-environment.…”

Gefitinib inhibits malignant melanoma cells through the VEGF/AKT signaling pathway

“…As one of the most important proangiogenic factors, VEGF is expressed in endothelial cells. It can promote vascular endothelial cell proliferation, differentiation, migration and movement, and form vessel structures by enhancing blood vessel permeability and degrading extracellular matrix (19). VEGF can promote neovascularization in tumorigenesis (20).…”