Replacing Molecular Testing With Next-Generation Immunohistochemistry: I Can Diagnose That Soft Tissue Tumor With a...

Immunohistochemistry plays a central role in the diagnosis of soft tissue tumors. Conventional immunohistochemistry uses antibodies directed against lineage-restricted antigens, in an attempt to identify a line of differentiation and narrow down the differential diagnosis. However, in most cases, such markers are inadequate to reach a specific diagnosis. Many soft tissue tumors harbor recurrent, often disease-defining molecular genetic alterations. Increasingly, fluorescence in situ hybridization analysis or next-generation sequencing is employed for identification of such alterations as a diagnostic adjunct. In recent years, immunohistochemistry has been used as a surrogate for such molecular genetic or cytogenetic analysis; this approach can identify the protein correlates of genetic alterations. Numerous next-generation antibodies directed against the protein products of a wide range of genetic alterations (such as gene fusions, amplifications, deletions, and point mutations) have entered our diagnostic armamentarium. In addition, gene expression profiling has uncovered diagnostically useful markers for immunohistochemistry. Finally, epigenetic alterations (eg, methylation) can also be assessed by immunohistochemistry. This review will provide examples of the application of contemporary molecular immunohistochemistry for soft tissue tumor diagnosis.