QUANTITATIVE AUTOMATED ANALYSIS OF CANCER MARKERS

The overall goal of this project is to develop systems that both 1) provide quantitative data for diagnostic/prognostic/predictive profiling in breast cancer and 2) detect micrometastases in lymph nodes and other tissue. The Ikonisys technology platform enables automated analysis of tests based on in situ hybridization and immunohistochemistry (IHC), providing quantitative data on amplification and/or expression of marker genes even in "rare" cells in a pathological sample. The Phase I project focuses on demonstrating the utility of the system using fluorescence in situ hybridization (FISH) to detect amplification of c-erbB-2; gene amplification has been shown to be a better prognostic/predictive indicator than protein overexpression for this important breast cancer marker. The detection and analysis system will be tested using 1) a commercially available c-erbB-2 FISH assay and 2) proprietary probes for c-erbB-2 and chromosome 17q (an internal control for aneuploidy). Validation experiments will be performed on clinical samples obtained by mammary excision and ductal lavage. The Phase II project will optimize the system for analysis of other breast cancer markers detected by in situ hybridization and IHC, then test its ability to aid in predicting clinical outcomes in breast cancer patients and detect micrometastases in lymph node tissue.