Blood Test Accurately Detects Lymphedema

Scientists have identified a set of proteins circulating in blood whose levels accurately flag the presence of lymphedema.

Lymphedema is an often-painful inflammatory condition resulting from the blockage of lymphatic vessels that ordinarily drain fluid from the tissues throughout the body. In the developed world, lymphedema usually arises as a consequence of radiation therapy for cancer. For example, about one in four breast-cancer survivors eventually develops lymphedema, said Stanley Rockson, MD,

For this study, Prof. Rockson and colleagues obtained skin-biopsy samples from both lymphedematous and normal tissue of 27 patients. Using molecular methods, they compared each patient's diseased tissue with that same patient's healthy tissue to see which were more actively engaged in the generation of their respective protein products in diseased versus healthy tissue. Then the investigators narrowed their search to the overproduced proteins themselves, in particular ones that were already known to circulate throughout the bloodstream of all people, including healthy ones, and for which fast, commercial blood tests already exist.

Statistical modeling indicated a panel of tests that measured six separate proteins' levels in study subjects' blood, was able to distinguish the lymphedematous patients from control subjects who did not have lymphedema. None of these six proteins was predictive by itself. But in aggregate, their presence at certain levels and ratios appeared to serve as a biological fingerprint, or biomarker, for lymphedema.

All six proteins are well known, and each is associated with one or another of chronic lymphedema's hallmark biological features: accumulation of fibrous deposits, stimulation of fat-cell activity, inflammation, and lymphatic-vessel formation and repair. "These biomarkers may themselves lead us to valuable pharmaceutical targets," said Prof. Rockson.

For validation of the six-protein biomarker panel the team collected blood from a new cohort of 36 lymphedematous and 15 healthy adults, extracted blood samples and tested them with the panel. The test distinguished those with lymphedema from healthy subjects with an accuracy approaching 90%, good enough for use as a clinical diagnostic tool and a vast improvement over current detection methods.

Levels of the six proteins begin to climb early in the course of the disease, thus such a test should be valuable in determining risk for, or the onset of, lymphedema long before symptoms occur. This would mean earlier, appropriate therapeutic intervention, perhaps in time to spare patients from the condition's most-damaging effects or even reverse its course.

The scientists, from Stanford University Medical Center (Stanford, CA, USA) have reported their findings reported in the December 18, 2012, issue of PLoS ONE.

Prof. Rockson said, "A standardized, accurate bioassay for lymphedema could help to pave the road for future human clinical trials of drugs to treat it." Monitoring trial subjects at the molecular level with a lymphedema-detecting blood test could provide early evidence regarding whether an experimental treatment is working.

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Stanford University Medical Center