The Combiome Hypothesis: Selecting Optimal Treatment for Cancer Patients.

Existing approaches for cancer diagnosis are inefficient in the use of diagnostic tissue, and decision-making is often sequential, typically resulting in delayed treatment initiation. Future diagnostic testing needs to be faster and optimize increasingly complex treatment decisions. We envision a future where comprehensive testing is routine. Our approach, termed the "combiome," combines holistic information from the tumor, and the patient's immune system. The combiome model proposed here advocates synchronized up-front testing with a panel of sensitive assays, revealing a more complete understanding of the patient phenotype and improved targeting and sequencing of treatments. Development and eventual adoption of the combiome model for diagnostic testing may provide better outcomes for all cancer patients, but will require significant changes in workflows, technology, regulations, and administration. In this review, we discuss the current and future testing landscape, targeting of personalized treatments, and technological and regulatory advances necessary to achieve the combiome.

Tissue handling and specimen preparation in surgical pathology: issues concerning the recovery of nucleic acids from formalin-fixed, paraffin-embedded tissue.

CONTEXT: Expression profiling by microarrays and real-time polymerase chain reaction-based assays is a powerful tool for classification and prognostication of disease; however, it remains a research tool, largely reliant on frozen tissue. Limiting the utility of expression profiling is the isolation of quality nucleic acids from formalin-fixed, paraffin-embedded tissue. The collection, handling, and processing of tissue directly impacts the biomolecules that can be recovered from it. High-quality nucleic acids can be obtained from formalin-fixed, paraffin-embedded tissue, but greater attention to all steps in the process of tissue handling and preparation is required. OBJECTIVE: To summarize the current state-of-the-art of preanalytic factors in tissue handling and processing as they impact the quality of RNA obtainable from formalin-fixed, paraffin-embedded tissue. The goals are to provide recommendations that will improve RNA quality for expression profiling from formalin-fixed, paraffin-embedded tissue and highlight areas for additional research. Tissue is an analyte and it must be handled in a standardized fashion to provide consistent results. DATA SOURCES: The literature was reviewed. Consultation with industry and academic leaders in the use of RNA for expression profiling was obtained to identify areas for additional research. CONCLUSIONS: Development of RNA-based assays from formalin-fixed, paraffin-embedded tissue is feasible. Greater attention to tissue handling and processing is essential to improve the quality of biospecimens for the development of robust RNA-based assays. Standardization of procedures and vigorous testing of alternative protocols are required to ensure that these assays function as designed.