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 HE-LVI 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 HE-LVI. 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.

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