Prognostic significance of lymphovascular invasion diagnosed by lymphatic endothelium immunostaining in breast cancer patients

Abstract

Prognostic factors for breast cancer include axillary lymph node status, tumor size, histology, nuclear grade, presence of estrogen and progesterone receptors, HER2/neu status, and mean microvessel density (MVD). In this study, we evaluated the usefulness of a new marker, D2-40, by investigating lymph vascular invasion of the tumor immunohistochemically in 132 patients with breast cancer and compared it with those of well-known prognostic indicators. Positive immunostaining of lymphatic endothelium with D2-40 outlining tumor emboli in the lumen of lymphatics was defined as D2-LVI, and lymphatic invasion following conventional hematoxylin and eosin staining was defined as HE-LVI. Significant correlation was observed between HELVI and D2-LVI (p<0.001), between lymph node status and HE-LVI (p=0.005), and between recurrent status and D2-LVI (p=0.008) by univariate analysis. Based on multivariate analysis, lymph node status (p<0.001, OR=6.993), tumor size (p=0.005, OR=5.504), D2-LVI (p=0.006, OR=4.740), and MVD (p=0.002, OR=4.484) were independent prognostic factors of disease recurrence. A significant difference in disease-free survival was also found between patients with and without D2-LVI (p=0.0067), but not with or without HELVI. Even in node-positive cases, D2-LVI had prognostic meaning. D2-LVI may play a crucial role for predicting recurrence of breast cancers much more than expected. Our data identifying D2-LVI expression in tumors of patients with a poor disease-free survival prognosis provides an easier and more accurate prognostic method than identifying HE-LVI.