Invasion and Cancer Stem Cell Biomarkers Can Predict Breast Cancer Metastasis
E Adler, M Oktay, R Stobezki, F Gertler, J Condeelis, J Jones, S Goswami. Montefiore Medical Center, Bronx, NY; Yeshiva University, New York, NY; Massachussetts Institute of Technology, Cambridge, MA; Albert Einstein College of Medicine, Bronx, NY; Weill Cornell Medical College, New York, NY
Background: Breast cancer mortality is largely attributable to the development of systemic, hematogenous metastatic disease. Currently established prognostic criteria such as the histopathological grade of the tumor or tumor size do not successfully predict systemic metastatic potential. Enrichment of cancer stem cells in the primary tumor is a known poor prognostic marker . Epithelial to Mesenchymal Transition (EMT) in breast cancer cells has been reported to give rise to cells having cancer stem cell like properties. Both of these cells types are highly invasive. We have identified invasion markers that can predict EMT, drug and radio resistance in breast cancer cells. Here we use biomarkers for cancer stem cells (CD44+/CD24- ) and markers of invasion Mena/Mena 11a to identify cancer initiating cells in Fine Needle Aspiration (FNA). We correlate these ratios with a microanatomical structure called Tumor Microenvironment of Metastasis (TMEM) comprising of a direct apposition of an endothelial cell, a cancer cell and a stromal macrophage in the breast cancer tissue. TMEM has been reported to strongly correlate with metastasis.
Design: FNA was performed on lumpectomy or mastectomy tissue using fine needle, quality was determined by smear staining. The cells were enzymatically digested, fixed, permeabilized and subjected to flowcytometry analysis using antibodies against stem cell and invasion markers. The rest of the tumor was processed for histopathology and TMEM analysis. Statistical analysis was done to identify correlation.
Results: Our initial results show that there is a strong correlation between CD44+/CD24- cells in the FNA with TMEM scores. We also report a very high correlation between TMEM scores and the ratios of different splice variants of Mena at the message level.
Conclusions: The percentage of CD44+/CD24- cells can be used to estimate the number of cancer stem cells in a FNA sample. The ratio of Mena/Mena 11a can be used as a measurement of tumor cell response to the microenvironment and its metastatic phenotype. Measuring the stem cell biomarkers and Mena isoforms in cells collected by FNA biopsy using FACS and combining that with TMEM density we will be able to develop a simple, quick and inexpensive method of determining metastatic potential of an individual tumor.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 8, Wednesday Afternoon