Evaluation of Angiogenesis Parameters and Tumor Markers in Inflammatory Breast Cancer Specimens

Inflammatory breast carcinoma (IBC) is an extremely rare, aggressive form of breast cancer that disproportionately affects young women. The risk factors and pathogenesis of these tumors are unknown and it is unclear whether tumors showing various clinical, pathological or molecular features behave differently. IBC appears to be a highly angiogenic tumor. In this study, tumor markers and parameters of angiogenesis will be further investigated in IBC.

The Inflammatory Breast Cancer Registry and Biospecimen Repository is a project funded by a grant from the Department of Defense to Paul H. Levine at GWUMC. The purpose of the registry is to develop a national registry of patients with IBC that will contain standardized clinical, epidemiological, and pathological information, along with recurrence and survival data. The goal is to obtain specimens from approximately 150 patients with IBC. The data in the registry and repository will be made available to researchers to aid in the development of a clinicopathological diagnosis of IBC. Investigators at GWUMC will consent recruited patients and collect clinical data. Subjects will not be recruited, evaluated, or monitored at the NCI. The GWUMC IRB will oversee human subjects protection issues. All samples obtained from GWUMC will be blinded and coded to the NCI investigators. In addition to the samples from George Washington University, we will obtain 150 control samples from the National Cancer Institute Cooperative Breast Cancer Tissue Resource. These samples were not available when this protocol was first submitted.

In collaboration with George Washington University Medical Center (GWUMC), we plan to test tissue specimens collected in the IBC registry and biospecimen repository. We will obtain frozen tissue (tissue and/or normal) and paraffin-embedded tissue blocks from each case. Genetic testing will not be performed on any of the samples. One pathologist reviews cases for grade and lymphovascular invasion (LVI) based on H& E staining. Specimens will be tested for biological markers associated with IBC to help in classification of these tumors. These include ER, E-cadherin, podoplanin, ReIB, RhoC and vasodilator-stimulated phosphoprotein (VASP). Angiogenesis parameters will also be evaluated. These include hypoxia-inducible factor 1 alpha (HIF-1 alpha), vascular endothelial growth factor D (VEGF-D) protein expression, VEGF-C protein expression, VEGF-receptor 2 (VEGFR-2, Kdr) or VEGF-receptor 3 (VEGFR-3, flt-4).