Abstract
Background: D2-40 is a mouse monoclonal antibody specific for human podoplanin and has been used in identifying lymphovascular invasion (LVI) of tumors; also its expression has been used as a marker for myoepithelial cells (MEC) of breast. Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalized tumor lymphovascular invasion (LVI). It also involves VEGF-C as the most important protein family. Lymphangiogenesis among breast cancer cases correlations with several clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and require clarification. Aim: The aims of this work (1) To explore the expression of D2-40 as a marker for myoepithelial cells (MECs) of the breast lesions, (2) To investigate the clinicopathological significance of VEGF-C, D2-40 expression and lympovascular density (LVD) in breast cancer patients. Methods: Sections from 88 paraffin-embedded archival specimens of breast lesions were selected to include benign breast lesions as fibrocystic changes of the breast and ductal hyperplasia (15 cases); and invasive breast cancer (73 cases). Immunohistochemistry (IHC) for D2-40, calponin and VEFG-C were performed and IHC staining results and the associations of intratumoral and peritumoral LVD were correlated with clinic-pathological features and prognosis were assessed. Results: D2-40 highlighted the MECs of benign breast lesions beside it identified lymphatic vessels and LVI in breast carcinomas. VEGF-C expression was significantly higher in invasive breast cancer than benign breast lesions (p < 0.01). VEGF-C (p < 0.001) expression was significantly associated with peritumoral LVD, but not intratumoral LVD. VEGF-C expression, peritumoral LVD and LVI were significantly associated with lymph node metastasis (p = 0.025, p = 0.006 and p = 0.017, respectively). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, disease-free survival in multivariate analysis. Conclusion: our results show that D2-40 is a reliable marker highlights MECs in benign breast lesions beside it is a useful tool for identification of LVI in breast carcinomas which reflecting a potential for lymphatic metastatic spread and possible poor prognosis. Our study also demonstrated that high expression of VEGF-C in invasive breast carcinoma may induce lymphangiogenesis in the peritumoral area. Peritumoral LVD appeared to be a potential
Highlights
The epithelial layer of normal breast and noninvasive breast tissues is surrounded by a layer of myoepithelial cells (MECs), whose absence or disruption is an absolute prerequisite for invasion and metastasis of the tumor [1]
D2-40 and calponin IHC labeled the MECs in their peripheral location along the breast lobules and terminal ducts in all the cases with strong intensity (Figure 1A and Table 1)
Our study demonstrated that MECs in benign breast tissues were positive for D2-40, and as expected, no MECs were found in invasive carcinomas by D2-40
Summary
The epithelial layer of normal breast and noninvasive breast tissues is surrounded by a layer of myoepithelial cells (MECs), whose absence or disruption is an absolute prerequisite for invasion and metastasis of the tumor [1]. D2-40 is a mouse monoclonal antibody specific for human podoplanin and has been used in identifying lymphovascular invasion (LVI) of tumors; its expression has been used as a marker for myoepithelial cells (MEC) of breast. Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalized tumor lymphovascular invasion (LVI) It involves VEGF-C as the most important protein family. Results: D2-40 highlighted the MECs of benign breast lesions beside it identified lymphatic vessels and LVI in breast carcinomas. Conclusion: our results show that D2-40 is a reliable marker highlights MECs in benign breast lesions beside it is a useful tool for identification of LVI in breast carcinomas which reflecting a potential for lymphatic metastatic spread and possible poor prognosis. Peritumoral LVD appeared to be a potential independent prognostic factor in breast cancer patients
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