Tumor invasiveness, not lymphangiogenesis, is correlated with lymph node metastasis and unfavorable prognosis in young breast cancer patients (≤35 years)

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Abstract

The morbidity rate of breast cancer is on the rise, and the age of onset appears to be trend-ing 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). Lym-phatic metastasis plays an important role in the spread of BCYW; however, the mecha-nisms 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 relation-ships between lymphangiogenesis, the expression of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) expression, clinicopathological charac-teristics, 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. How-ever, in BCMEW, MMP-9 expression was not correlated with LNM or survival time. In addi-tion, 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 analy-sis showed that MMP-9 expression and LNM were independent prognostic factors in BCYW. Our present study indicates that lymphangiogenesis induced by VEGF-C is aug-mented in breast cancer; however, a higher level of lymphangiogenesis has no significant PLOS ONE |

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Zhang, Z. Q., Han, Y. Z., Nian, Q., Chen, G., Cui, S. Q., & Wang, X. Y. (2015). Tumor invasiveness, not lymphangiogenesis, is correlated with lymph node metastasis and unfavorable prognosis in young breast cancer patients (≤35 years). PLoS ONE, 10(12). https://doi.org/10.1371/journal.pone.0144376

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