Pathology, Biomarkers, and Molecular Diagnostics
Summary of Key Points
• Biomarker development has profoundly affected basic understanding of carcinogenesis and expanded means of intervention in human cancers. Biomarkers have been applied with variable success in three broad areas that correspond to phases of tumor development and progression: (1) early detection, (2) diagnosis, and (3) prediction of clinical outcome (prognosis) and response to targeted treatment.
• For early detection, biomarkers go through five stages of development: (1) identification of promising directions; (2) validation of a clinical assay; (3) demonstration that the biomarker can detect disease before it is clinically relevant; (4) evaluation of the biomarker during prospective screening; and (5) quantification of the effect of screening on reducing the burden of disease in a population.
• Early detection using quite different approaches has changed the natural history of cervical, colorectal, and lung cancer. Progress depends on improving our understanding of the biology of site-specific carcinogenesis and using intervention strategies informed by basic biology.
• Cancer diagnosis still relies on an evaluation of tumor tissue histology, a complex process associated with interindividual variation; however, new approaches to automated quantitative histologic evaluation and immunohistochemical analyses are under active development.
• New molecular diagnostic approaches that utilize assessment of quantitative messenger RNA signatures, fluorescent-in-situ hybridization, quantitation of microRNAs, and genetic sequencing can now be accomplished with accurate use of formalin-fixed paraffin-embedded tissues.
• Molecular testing can provide guidance in prioritizing therapies for patients most likely to benefit and can identify patients who have been proven not to benefit from a targeted therapy.
• Molecular testing can also provide clinicians with a rationale to guide specific patients toward specific clinical trials.
• As new molecular techniques have been applied to cancer diagnosis and treatment, the necessity of developing standardized processing approaches for solid tumor specimens has been appreciated and has helped to change tissue collection and specimen-handling routines.
