The biological markers of non-Hodgkin's lymphomas: their role in diagnosis, prognostic assessment and therapeutic strategy.

The biological markers of non-Hodgkin's lymphomas (NHL) are distinguished in three categories: serological, immunophenotypic, and molecular markers. The clinical importance of biological markers in NHL is based on their support of morphologic diagnosis, their role in staging and prognostic assessment, and their contribution to monitoring minimal residual disease (MRD). The most important serological markers reflect the tumor load (beta-2 microglobulin, beta 2-M), proliferative activity (lactic dehydrogenase, LDH), and invasive potential of lymphomas (CA 125). LDH and beta 2-M are included as important prognostic parameters in widely used staging systems. Immunophenotypic analysis identifies specific markers of lineage (B or T-cells), maturation level, cell proliferation, and clonality. Results of immunophenotyping are particularly useful in low to intermediate-grade NHLs to support the morphologic diagnosis and facilitate the detection of MRD after treatment. The molecular markers are genetic lesions involved in the pathogenesis of some categories of NHL. Their use as markers for diagnosis is justified by the selective association with specific lymphoma categories: follicular, mantle cell, diffuse large cell, and anaplastic large cell lymphomas. Molecular lesions are the most specific and sensitive markers for evaluating MRD. Today the biological markers of NHL are widely employed for diagnosis, staging, and prognostic assessment. Their systematic use may complement clinical parameters in the stratification of NHL patients, who may thus become candidates for treatments of different intensity. The detection of MRD after first-line treatment identifies patients at high risk of relapse who require additional therapy to cure their disease.