Nanomechanical profiling of human breast tumors as prognostic marker for breast cancer.

Abstract

11618 Background: Assessment of tumor aggressiveness is crucial when making treatment decisions. Established prognostic markers may be insufficient to stratify cancer patients into treatment relevant risk groups. Emerging evidence indicates mechanical properties of cancer cells and their microenvironment play a vital role in cancer invasion and metastases. Detecting and measuring these nanomechanical changes could be a marker of cancer aggressiveness. Methods: We developed an atomic force microscope (AFM) based method: ARTIDIS (Automated and Reliable Tissue Diagnostics) for measuring nanomechanical properties of human tissue biopsies. These were performed on fresh, non-fixed tissue under physiological conditions. This novel method uses a micro-fabricated 20nm tip indenting and measuring stiffness of thousands of locations within 60-180minutes. This quantitative, biopsy-wide, nanomechanical profile strongly correlates to the tissue's biological composition. Post-AFM this biopsy is analyzed by pathology. We sought to differentiate benign from cancerous lesions based on nanomechanical properties; then link the cancerous nanomechanical profiles prospectively to the clinical outcomes. Results: Our results demonstrate the first AFM based nanomechanical profiling to detect aggressive breast cancer subtypes using fresh tissue in a clinical setting. We have shown that nanomechanical profiles of human breast cancer biopsies display stiffness profiles distinct from surrounding normal tissue. Breast cancer subtypes were distinguishable by their nanomechanical properties only. We have discovered specific nanomechanical profiles of tumor subtypes likely to metastasize. When the primary tumor displayed the same soft nanomechanical profile as adjacent tissue, this was associated with positive nodal status. Conclusions: Our results demontrate nanomechanical profiling is a fast and sensitive method to stratify malignant biopsies into relevant subgroups in a clinical setting. Relative stiffness and distribution values provide a nanomechanical profile indicating cancer aggressiveness. This will help optimize specific cancer diagnosis, orientate therapy choice and support patient follow up.