New Test Can Help Predict Aggressive Cancers
Lotan and De Marzo hope the test for PTEN loss will become an
important part of the diagnosticarsenal for prostate cancer PTEN is a pretty important gene. It's a tumor suppressor, which means that it helps prevent the out-of-control cell growth that can lead to cancer. "It acts like the brakes on a car for cancer cells," says urologic pathologist Angelo De Marzo, M.D., Ph.D., whose laboratory has been studying this gene's loss in prostate cancer for nearly a decade. When PTEN is knocked out – as it is in about half of lethal prostate tumors – cancer cells behave more aggressively. "The loss of PTEN leads to uncontrolled cancer cell growth, and the prevention of cancer cell death. PTEN is one of the few genes whose loss has been consistently associated with aggressive prostate cancer."
Compared to FISH, the new test is less expensive, faster, and much easier for pathologists to interpret. New studies led by Lotan with De Marzo and others at Hopkins suggest this new PTEN test, based on a relatively simple immunohistochemistry, or IHC, assay, is nearly ready for widespread routine use. In a study of radical prostatectomy patients followed closely for many years by Patrick Walsh, M.D., Lotan evaluated a large number of tissue specimens using a technology called "high throughput Tissue Micro Array." Using the IHC test, she discovered a strong correlation between the loss of PTEN and the signs of aggressive prostate cancer, including the Gleason grade of the tumor as well as the stage of the tumor and the time it took for metastases to develop; this work was published in Clinical Cancer Research. In a larger follow-up study published in Modern Pathology, Lotan and De Marzo, along with pathologist George Netto, M.D., urologist Misop Han, M.D., and epidemiologist Elizabeth Platz, Sc.D., M.P.H, the IHC test found that PTEN loss correlated with faster recurrences after radical prostatectomy, "again indicating a link between PTEN loss in tumors and aggressive behavior," notes De Marzo.
In another study recently published in Modern Pathology, Lotan, along with De Marzo and Jonathan Epstein, the Rose-Lee and Keith Reinhard Professor in Urologic Pathology, showed that the PTEN test can help pathologists identify an important subtype of non-invasive tumor called intraductal carcinoma of the prostate. Intraductal cancers spread in ducts within the prostate and don't venture outside the gland, but they keep bad company: "They have been known for years to be associated with highly aggressive and often deadly invasive prostate cancers," she says. Intraductal cancers are often difficult for pathologists to diagnose under the microscope, but Lotan has shown that these tumors have almost always lost PTEN, and she believes that this finding may help pathologists "better recognize these tumors and identify men who are at risk for developing metastases and lethal prostate cancer."
PTEN is one of the few genes
"Putting together all of these findings over the last several years," says De Marzo, "it is clear that there is compelling clinical evidence that PTEN loss is associated with aggressive prostate cancer, which is paving the way for the ultimate widespread use of the PTEN IHC test in the clinic for men with low- to intermediate-risk prostate cancer."