Immunohistochemical Surrogates for Genetic Alterations of CCDN1, PML, ALK, and NPM1 Genes in Lymphomas and Acute Myeloid Leukemia

The World Health Organization (WHO) classification of lympho-hemopoietic neoplasms is increasingly based on genetic criteria. Detection of tumor-associated primary genetic lesions is usually performed using the polymerase chain reaction (PCR) and/or fluorescence in-situ hybridization (FISH). This review focuses on alternative techniques for detecting genetic lesions in biopsy samples. Immunohistochemical surrogates for the detection of genetic alterations involving the CCND1, PML, anaplastic lymphoma kinase (ALK) and nucleophosmin (NPM1) genes are presented as examples for this approach. Because of their high specificity, rapidity, low costs and ease of performance, these assays have the potential for being extensively applied in developing countries. In some instances (e.g. detection of ALK protein) immunohistochemistry has fully replaced molecular studies for routine diagnosis in paraffin-embedded specimens. Genome wide based discovery of new tumor-associated genetic lesions that are suitable for antibody targeting promises to further expand the application of immunohistochemistry for the molecular classification of hematological neoplasms.