In developing biomarkers (BM) to determine the likelihood that initial breast tumor remains contained in situ, as opposed to becoming invasive. In-tissue testing serves as a gold standard for breast cancer diagnostics, yet the power of high throughput technologies can be realized for diagnostic purposes if emerging technologies can be directly applied to samples obtained by the routine clinical procedure. Although a variety of quantitative
methods exist for assaying biofluid-based BM, contemporary proteomic technologies remain impractical for application to archived formalin-fixed paraffin--embedded (FFPE) tissues that (being associated with clinical histories) provide a trove of information for BM discovery. Immunohistochemistry (IHC) remains the tool of choice to examine protein expression in tissue; however, it does not lend itself to the truly continuous measurements needed for BMstudy. We developed the analytic tools and algorithms â without use of sophisticated and expensive equipment-that allow measurements of protein expression in FFPE tissue on a continuous biologically relevant scale, while quantification of relative (rather then absolute) intensity of staining takes into account fluctuations of background staining. Using this approach, we have revealed that women with invasive breast cancer were 4 times more likely to have increased levels of insulin-like growth factor type I receptor and its target, Ras-related protein 1 than women with non-invasive tumors. To facilitate development of novel in--tissue BMs, we are taking advantage of digital multispectral imaging technology and developing pattern-recognition-based image analysis for the core-needle biopsies containing early form of breast cancer, i.e. carcinoma in situ.
Last date updated on July, 2014