Prognostic Value of Lymphocyte Vascular Density and E-Cadherin in Inflammatory Breast Cancer

Paul H Levine,Salman Hashmi,Kenneth L Van Golen,Sherry X Yang,Sandra M Swain,Audra Macneil,Stephen Hewitt,Heather J Hoffman

doi:10.4236/jct.2014.514139

Abstract

Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients. Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and survival data were available for up to 17 years. Overall survival (OS) was analyzed through the Kaplan-Meier method stratified by E-cadherin, LVD, VEGF-D, and response to chemotherapy. The differences in OS curves were compared using the log-rank test. Results: The median OS for patients with high LVD was 6.63 years (95% CI: 4.06 to 10.14), compared to median at 10 years not reached in those with low LVD (p = 0.03). There was a trend towards a longer median OS in patients with high E-cadherin (10.14, 95% CI: 6.63 to 11.67), compared with those with low E-cadherin (6.26, 95% CI: 3.42 to undeterminable). VEGF-D levels showed no correlation with survival. Conclusion: Low LVD significantly predicts better survival. High E-cadherin expression, as with non-IBC breast cancer and several other malignancies, tends to be associated with a better prognosis.

Highlights

Inflammatory breast cancer (IBC) is an unusual form of breast cancer marked by aggressiveness and biological behavior with a tendency to disseminate micrometastases from the outset rather than develop in a more controlled stepwise progression as seen in most carcinomas
50% of the IBC patients had a low E-cadherin level (
A multiple comparison test of E-cadherin and response to treatment was statistically significant (p = 0.016), so higher E-cadherin and better response to chemotherapy was associated with increased survival probability (Figure 2(b))

Summary

Introduction

Inflammatory breast cancer (IBC) is an unusual form of breast cancer marked by aggressiveness and biological behavior with a tendency to disseminate micrometastases from the outset rather than develop in a more controlled stepwise progression as seen in most carcinomas. We recently evaluated several potential prognostic markers in a study assessing laboratory markers differentiating IBC from LABC, VEGF-D, E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE) [3]. With the advantage of a long follow-up of the IBC patients in our IBC registry, we investigated the prognostic value of the three quantitative assays in determining long-term survival in IBC. We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients.

Methods

Results

Discussion

Conclusion