Advances in molecular and cell biology have provided us with an understanding of the mechanisms of disease at the molecular and genetic levels. This understanding can now be translated into diagnostic, prognostic, and therapeutic applications in modern medicine. Abnormal molecules not only provide a signature for the presence of a disease, but may also provide the indication for a drug targeting the specific abnormal function. Concurrently, the role of diagnostic pathology has expanded from mere morphologic observation into comprehensive tissue analysis through combined histological, immunohistochemical and molecular evaluations. Yale Pathology’s program in Molecular Diagnostics is constantly translating new discoveries and novel technologies into useful clinical tests that provide a molecular fingerprint of diseases and that are predictive of the response.
At Yale Pathology, one of the preeminent areas of application of molecular diagnostic testing is oncology. It is now possible to phenotype and genotype human tumors to increase the accuracy and reproducibility of pathologic diagnosis. Small numbers of malignant cells can be detected in cytological preparations or biopsies through the clinically validated use of molecular markers. The detection of clonally rearranged antigen receptor genes in lymphoid cells is a powerful tool for establishing a lymphoma diagnosis. In addition to establishing primary diagnoses, genotyping can effectively detect minimal residual disease and classify lymphoma subtypes. Somatic genetic alterations of solid tumors have also been found useful in clinical applications. Characteristic mutations can be used as markers for the detection of very small numbers of tumor cells (endoscopic biopsies or fine needle aspirates) to increase the sensitivity and accuracy of pathologic diagnosis. In specific instances (e.g. selected soft tissue and pediatric tumors), specific fusion gene transcripts provide a basis for molecular diagnosis and subclassification. Tissue DNA genotyping has recently been validated at Yale Pathology as a highly practical and cost-effective method for the routine diagnosis and sub-typing of molar pregnancies.