Even after patients have undergone a radical prostatectomy, which removes the regional draining lymph nodes of the prostate, hidden tumor cells can still exist. These cells can result in cancer recurrence. Current routine methods, which include blood tests, radiographic techniques, and histological exams by pathologists, may not be able to find these cells. The USC test detects hidden metastases in early-stage cancer patients not detectable by traditional methods.
“We've examined the lymph nodes that were originally called negative [i.e., not containing cancerous cells] by a pathologist and showed that 13% of those test subjects had tumor cells that weren't detected,” says Richard Cote, MD, professor of pathology and urology at USC's Keck School of Medicine.
The test is a result of nearly 20 years of research at Cote's lab. It uses a general assay method, called immunohistochemistry, and commercially available antibodies. During the test, researchers take routine pathology tissue, which is a paraffin block containing lymph nodes, cut additional slides from the tissue, and subject it to an immunohistochemical assay. Researchers then apply antibodies that are specific for epithelial cells in one case, and prostate cells in another case. Cancerous cells will react with antibodies to cytokeratins and prostate-specific antigen. The latter is a protein made by cells in the prostate gland.
“[The test] finds the presence of cells in a place where they don't belong. [It indicates whether the cancer] has spread, or metastasized,” says Cote. “Metastasis is the key event in cancer—it's the reason cancer is dangerous.”
According to Cote, the test could be used in its present form and developed into a commercial diagnostic test. Although Cote developed the prognostic test in his lab, it isn't patented and could be easily adapted in a commercial setting. It could also be integrated with other tests, and Cote advises that it be used in conjunction with other methods of analysis. “We would recommend that this be part of the evaluation of patients with early-stage prostate cancer, but not the only thing that should be done. The histologic analysis and the tumor grating, the kinds of things we normally do, must remain part of the evaluation process.”
The USC researchers have already used the test to explore other areas of cancer detection. The group's first studies involved breast cancer and were published in 1999. Current studies are using the test to detect metastases in bone marrow and lymph nodes for breast and lung cancers.
The test has a lot of promise in disease detection. “We have a whole program devoted to this technology, both for the detection in lymph nodes and blood and bone marrow, which includes immunohistochemistry and molecular techniques, as well as a program that involves sophisticated separation devices that use microfluidics and nanotechnology,” says Cote.
The National Institutes of Health, the National Cancer Institute, Department of Defense, and the California Cancer Research Program provided grants for Cote's work.