Diagnostics & Imaging Week
The microscope was a huge step forward in distinguishing between the morphological distinctions between similar disease states. Today, genetic analysis is pushing this critical ability into an even larger realm of precision.
The National Cancer Institute (NCI) of the National Institutes of Health (NIH; both Bethesda, Maryland) reported last week that a team of researchers, including several from the NCI, has found that gene expression profiling can "accurately distinguish between two types of immune cell tumors" – Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL)
The NCI said that while each of these lymphomas appears similar when viewed under a microscope, "correct diagnosis is critical" because each cancer requires very different treatments.
The findings were published in the June 8 issue of the New England Journal of Medicine. And as a result of the findings, the NCI hopes ultimately to license the technology to develop a clinical DNA test to "diagnose all types of lymphoma," Louis Staudt, MD, PhD, deputy chef of the Metabolism Branch and head of the Molecular Biology of Lymphoid Malignancies Section in NCI's Center of Cancer Research, told Diagnostics & Imaging Week.
"The real question is, when can we bring this to patients and their care?" Staudt said, noting that this is a goal that "everybody is also working on very diligently."
While he said clinical use might be achieved "in roughly a couple of years," clinical trials and FDA approval would first be necessary.
NIH Director Elias Zerhouni, MD, said genetic profiling is emerging "as a powerful new tool for determining treatment choices. In the future, many tumors 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."
John Niederhuber, acting director of the NCI, said: "We are beginning to have the ability to take microscopically identical tumors from different patients and demonstrate that they are genetically distinct, in order to provide greater certainty about diagnosis and prognosis."
While not all cases of these two lymphomas are morphologically similar, using standard pathology examination, some cases "can be very difficult" to distinguish, said Staudt, also a research team co-leader for the Burkitt's study.
The difference in disease outcome depends greatly on a patient's receiving the appropriate therapy, so accurate diagnosis between the two lymphomas is essential.
"If Burkitt's patients are treated with intensive therapy, there is roughly an 80% survival rate," Staudt said. "However, if they are misdiagnosed and treated with the therapy recommended for DLBCL, lower intensity chemotherapy, the survival is reversed to 20% or even less."
The current standard for diagnosing these lymphomas is "a combination of the morphological appearance under the microscope of the malignant cells and the presence or absence of certain protein biomarkers by immunohistochemistry," Staudt said.
Molecular profiling of various types of cancer "really began about six years ago," he said, noting that it is "not a new field." And progress continues to be made.
Burkitt's lymphoma and DLBCL are types of non-Hodgkin's lymphoma, a malignancy of B lymphocytes, a type of white blood cell. The NCI said that Burkitt's lymphoma is seen primarily in children, but can affect adults age 30 to 50. DLBCL can affect people of any age, the NCI said, but is most often found 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 NCI said.
To carry out their study, investigators collected samples of Burkitt's lymphoma from institutions in the U.S., Canada and Europe. Those 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.
Burkitt's lymphoma samples were then evaluated by a panel of expert hematopathologists using "the latest diagnostic methods," the NCI said. They reclassified the samples into the following categories: Burkitt's lymphoma, atypical Burkitt's lymphoma, DLBCL and high-grade lyphomas.
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 that diagnosis 100% of the time. However, among samples reclassified as DLBCL, molecular profiling identified 35% as Burkitt's lymphoma.
Overall, the NCI said that the study "suggests that 17% 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 agency said an estimated 58,800 people would be newly diagnosed with NHL in the U.S. in 2006. An estimated 19,000 will die of the disease.