Prostate Cancer Diagnosed by Tumor DNA in Blood

The 'Molecular Diagnostics' issue of Clinical Chemistry, the journal of AACC, features new research on a genetic test for prostate cancer that could replace the unreliable prostate specific antigen (PSA) test, as well as a more accurate test for breast cancer drug resistance. Both tests could help patients receive more targeted treatment for prostate and breast cancer, which in the U.S. are the second leading causes of cancer death in men and women, respectively.

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New Research Shows Tumor DNA can be Used to Diagnose Prostate Cancer

Though the prostate specific antigen (PSA) test is the most widely used blood test for prostate cancer, it has a surprisingly low accuracy rate—approximately 25%. A team of researchers led by William M. Mitchell, MD, PhD, of Vanderbilt University, Nashville, Tennessee, set out to determine whether analyzing cell free tumor DNA found in a patient’s blood for missing and/or extra gene copies—a hallmark of almost all cancer types—could yield more reliable results.

When tumor cells undergo cell death, they release DNA—now considered cell free—into the blood. By sequencing the cell free DNA of 204 prostate cancer patients, Narod’s team identified 20 regions in the patients’ chromosomes that exhibited a high number of missing and/or extra gene copies, and also contained a large proportion of cancer-related genes. The researchers determined that the presence of these 20 regions distinguishes prostate cancer patients from healthy individuals with an accuracy of 83%. This model can also distinguish prostate cancer from benign prostatic hypertrophy and prostatitis, two non-cancerous conditions that lead to false-positive PSA test results—with an accuracy of 90%.

Drug-resistant tumor cells are one of the major causes of chemotherapy failure in breast cancer patients, with 30–40% of patients with estrogen receptor-positive breast cancer (the most common type) exhibiting resistance to the anti-hormone therapies used as treatment. A group of researchers led by Shulin Li, PhD, of the University of Texas, Houston, investigated measuring levels of circulating tumor cells—or cancer cells found in the blood—as a way to predict patient response to treatment and enable doctors to tailor chemotherapy regimens.

A characteristic of drug-resistant cancer cells is epithelial-mesenchymal transition (EMT), a process that leads to epithelial cells gaining migratory and invasive properties. To date, however, the only method cleared by FDA for counting circulating tumor cells detects epithelial circulating tumor cells, but not those undergoing EMT. In a pilot study involving 58 metastatic breast cancer patients, Li’s team developed and validated a first-of-its-kind test that uses detection of cell-surface vimentin (CSV)—a protein found on EMT circulating tumor cells—to count a patient’s EMT circulating tumor cells. The researchers then used the sum of a patient’s EMT circulating tumor cells and epithelial circulating tumor cells to distinguish between drug-resistant and -responsive patients with a high sensitivity of 92.5%.

“Because [circulating tumor cells] are heterogeneous cells with both epithelial and mesenchymal (EMT) phenotypes, it is very important that we take both of these populations into consideration when analyzing the therapeutic response of different chemotherapeutic regimens in patients,” writes Dr. Li. “In this age of biologically targeted therapeutics, we can take advantage of this dual system to detect, isolate, and characterize [circulating tumor cells] of different phenotypes simultaneously, which may be key in supplying vital information for personalized medicine in breast cancer.”

About AACC
Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of breaking laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation.

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Source: AACC

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