[380] 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.

Comparison of HER2 expression in primary tumor and CTCs
 Primary TumorCTC
HER2 +1416
HER2 -20

The HER2 status of the metastases when available was reported to be similar to that of the primary tumor. All HER2 reported as 1+ or 2 + in surgical samples were not amplified by FISH.The HER2 expression of primary tumors matched that of the CTCs in 14 of 16 cases. In two cases the HER2 of the primary tumor was negative with HER2 -positive CTCs.
Conclusions: The CTC phenotype may accurately reflect the tumor phenotype than expression in the primary or metastatic sites. Immunohistochemical (IHC) evaluation of HER-2 protein by chromogenic IHC is not only subjective and semiquantitative, but has intrinsic variables. We hypothesize that the HER-2 expression in CTCs may be true reflection of metastatic clone derived from the primary tumo and may predict response to targeted therapy despite the negative HER2 expression in the primary tumor.
Category: Cytopathology

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 91, Wednesday Afternoon


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