Correlation of Expression of HER2 in Circulating Tumor Cells and in Corresponding Primary Tumors in Breast Cancer Patients.
Malini Harigopal, Philip Galullo, Gillian Levy, Pei Hui, Diane Kowalski, David L Rimm, David Chhieng. Yale University School of Medicine, New Haven, CT
Background: Enumeration of circulating tumor cells (CTCs) is a rapidly growing new diagnostic test to help manage oncology patients. The prognostic importance of monitoring CTCs levels for recurrence and response to chemotherapy in breast cancers has been shown by prior studies. These assays also have the potential benefit to guide treatment decisions based on the molecular profile of the tumor before therapy. A positive HER2 status is associated with aggressive tumor behavior. We propose to determine the differential protein expression of HER-2 in the primary tumors and CTCs.
Design: Whole blood was drawn from patients with metastatic breast carcinoma (n=323) The CellSearch System (Veridex,LLC,Warren,NJ) the only FDA approved technology was used to analyse CTCs which consists of a semiautomated sample preparation system and the CellSearch Epithelial Cell kit to immunomagnetically enrich cells expressing epithelial cell adhesion molecule. Circulating tumor cells are defined as intact tumor cells that express the epithelial cell marker (CK-PE) with a nucleus that stains positive for the nucleic acid dye (Dapi) and are negative for the leukocyte marker CD45. CTC analysis were done by cytotechnologists and pathologists certified by Veridex.
Results: CTCs were detected in 44% of metastatic breast cancer patients with frequency range of 1-701, mean 7.1, SD=44. CTCs were investigated for HER2/neu in 20 cases. HER2 -positive CTCS were present in 16 cases with a frequency range of 1-224, mean 2.5, SD=44. HER2 expression of primary tumors as assessed by clinical immunohistochemistry were compared to CTCs HER2 expression.