Gene expression profiling, a molecular technique that analyzes many genes simultaneously, can accurately distinguish between two types of immune cell tumours -- Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) -- according to a team of researchers*, including several from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

Burkitt's lymphoma and DLBCL cells appear similar when viewed under a microscope but correct diagnosis is critical because each cancer requires very different treatments. Study results appear in the June 8, 2006, issue of the "New England Journal of Medicine".

"This is an example of how genetic profiling is emerging as a powerful new tool for determining treatment choices," said NIH Director Elias A. Zerhouni, M.D. "In the future, many tumours will be classified using genetic profiling, and treatments will be tailored to meet the needs of each patient, another example of a more predictive and personalized era of medicine."

"For the first time, we are beginning to have the ability to take microscopically identical tumours from different patients and demonstrate that they are genetically distinct, in order to provide greater certainty about diagnosis and prognosis," said NCI Acting Director John E. Niederhuber, M.D. "A complete genetic analysis of human cancers will provide us with the ability to match the patient with a highly specific regimen of targeted therapies."

Burkitt's lymphoma and DLBCL are types of non-Hodgkin's lymphoma (NHL), a malignancy of B lymphocytes, a type of white blood cell. Healthy lymphocytes help destroy bacteria, viruses and other infectious agents invading the body. Burkitt's lymphoma is seen primarily in children, but can affect adults ages 30 to 50. DLBCL can affect people of any age; it is most often observed in adults 60 years or older. Because both lymphomas can occur in the same age group and patients present similar clinical symptoms, it is often difficult to distinguish these two types of NHL.

"The value of molecular profiling to accurately diagnosis Burkitt's lymphoma versus DLBCL will have a major impact on patients because the treatment for these two lymphomas is very different," said Louis Staudt, M.D., Ph.D., deputy chief of the Metabolism Branch and head of the Molecular Biology of Lymphoid Malignancies Section in NCI's Center of Cancer Research, as well as research team co-leader. "If Burkitt's patients are treated with intensive therapy, there is roughly an 80 percent survival rate. However, if they are misdiagnosed and treated with the therapy recommended for DLBCL, lower intensity chemotherapy, the survival rate is reversed to 20 percent or even less."

To carry out their study, investigators collected samples of Burkitt's lymphoma from institutions in the United States, Canada and Europe. These organizations are part of the Lymphoma/Leukemia Molecular Profiling Project, an NCI research collaboration. A total of 71 samples were obtained from previously untreated patients who had been diagnosed as having Burkitt's lymphoma or atypical Burkitt's lymphoma. (Atypical Burkitt's lymphoma tumours have the characteristic genetic and proteins markers associated with Burkitt's lymphoma, but not the classic microscopic appearance.)

Burkitt's lymphoma samples were then evaluated by a panel of expert hematopathologists using the latest diagnostic methods. They reclassified the samples into the following categories: Burkitt's lymphoma, atypical Burkitt's lymphoma, DLBCL and high-grade lymphomas. The review panel reclassified nearly one-third of the samples originally diagnosed as Burkitt's lymphoma, demonstrating the difficulty in making an accurate diagnosis.

All samples underwent molecular profiling using DNA microarrays -- a technique that simultaneously measures the activity of thousands of genes expressed in a single sample. Among the samples declared to be Burkitt's lymphoma by the review panel using standard pathological methods, molecular profiling correctly predicted this diagnosis 100 percent of the time. However, among samples reclassified as DLBCL, molecular profiling identified 35 percent as Burkitt's lymphoma. Overall, this study suggests that 17 percent of the cases of Burkitt's lymphoma may have been misdiagnosed using standard pathological methods, which would result in inappropriate treatment for these patients.

"The distinction between Burkitt's lymphoma and DLBCL was easy to make based on the molecular profiles," said John Chan, M.D., professor, Nebraska Medical Center in Omaha, Neb., and study co-leader. "The power of molecular profiling is providing additional information when cases are difficult to diagnose. Eventually we hope this type of analysis will help us understand the molecular mechanisms causing this disease and identify novel targets for therapeutic interventions."

This study underscores the value of molecular profiling in diagnosis of Burkitt's lymphoma; however this is an experimental test and will require further development before it is available for clinical use.