Conclusion

Clinical demand for genetic characterization of BCL at the time of primary diagnosis has intensified as our understanding of NHL biology has increased and therapies targeting specific BCL have been developed. Today, genetic features of NHL are used to aid in rendering an accurate primary diagnosis, to predict prognosis, to evaluate for MRD after therapy, and even to help determine optimal therapy. The rapid acquisition of knowledge about BCL biology and translation of this knowledge into targeted therapeutic strategies is occurring today at an unprecedented rate. New testing strategies and technologies are essential for clinical laboratories to keep up with the growing information on BCL obtained from research methods such as gene expression profiling, comparative genomic hybridization, and proteomics.

Clinical laboratories doing molecular testing on BCL today are faced with two daunting tasks. First and foremost is the necessity of expanding test menus to meet the increasing clinical demand for testing for new genetic markers in NHL. Expanding test menus to meet clinical needs will require technical advances, as the current technology in clinical molecular laboratories does not allow rapid screening of BCL for a broad panel of relevant genes at a reasonable cost. Permutations of research methods are under development and show promise in alleviating the technological bottleneck preventing translation of this new genetic knowledge to the clinical laboratory. However, the lack of a reasonable level of reimbursement for molecular testing in general is a major roadblock to successful implementation of new techniques for molecular testing for important new genetic markers in BCL.

The second task facing clinical molecular laboratories, which is equally important to the credibility of the field, is the urgent need for standardization of molecular testing methods to eliminate the wide variability of results among molecular laboratories. Laboratories in Europe are ahead of those in the United States in standardizing molecular testing for lymphoma and leukemia clinical treatment trials, partly because of the substantial government support they have had to accomplish this task and partly because of their geography. It is likely that similar governmental support, probably linked to mandated proficiency testing, will be needed to achieve a comparable level of laboratory standardization of molecular testing in the United States. If molecular laboratories in the United States do not voluntarily develop a format for standardization of clinical molecular testing for leukemias and lymphomas, it is likely that hematopathology molecular testing in the future will be confined to large central reference laboratories.

The role of the molecular hematopathologist is clearly changing and expanding. As genomic profiling, comparative genomic hybridization, and other genomewide screening research identifies more new genes and biologic mechanisms that play important roles in the therapeutic responsiveness and overall survival of lymphoma patients, clinicians are beginning to incorporate this new knowledge into the selection of more targeted therapies. Clinical molecular laboratories performing hematopathology molecular diagnostic testing today must provide input at the time of initial diagnosis and during the course of treatment to ensure the performance of appropriate molecular testing and the accurate interpretation of results. The testing performed to confirm initial diagnosis and evaluate for prognostic genetic abnormalities in BCL is not the same testing that will be performed for detection of MRD after therapy. Furthermore, the lines between classical cytogenetics laboratories and molecular laboratories are blurring, due to the marked increase in the use of molecular probes for FISH analysis. Molecular pathologists increasingly will need to be very familiar with both lymphoma biology and different therapies for lymphoma, and will have to interact more closely with clinicians than ever before to accurately interpret the results of molecular tests.

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