Looking to Identify Men with High-Risk Prostate Cancer Early

Robert Veltri, PhD

Some men are diagnosed with small, low-risk prostate cancers and choose active surveillance. "However, some of these low-risk cancers may harbor molecular or other very subtle nuclear morphological features of size & shape in more aggressive cancer," says Robert Veltri, Ph.D., Associate Professor of Urology and Director of the Fisher Biomarker and Repository Laboratory at the Johns Hopkins University School of Medicine. "If these men could be identified early, we could eradicate their cancer when the disease burden is low." Morphologic features refer to the size, shape and consistency of the nucleus (or center) of a given cell.

The red flags that signal more aggressive disease early-on are extremely tiny, for example, subtle nuclear morphological alterations within the cancer cell, or differences in the levels of specific cancer-related proteins. Veltri, working with Brady Urology Institute urologists, Alan Partin, M.D., Ph.D. and H. Ballentine Carter, M.D.; and a world's expert pathologist, Jonathan I. Epstein, MD, has used highly sophisticated methods to analyze very small prostate biopsy tissue samples for ways of identifying men who appear to have more aggressive disease. Dr. Veltri is looking for a "signature" of aggressive disease that can be spotted at a diagnostic biopsy and his research is funded by the Early Detection Research Network of the National Cancer Institute and a Department of Defense.

Morphology versus morphometry for adenoma assessment. Morphometric measurements performed by quantitative, digitalized assessment of histopathology slides compared with regular pathology assessment through the microscope.  From http://www.medscape.com/viewarticle/703573_5 

Previously, Dr. Veltri demonstrated that DNA content of cancer cells and the levels of (-7)ProPSA (a precursor molecule to PSA) in biopsy tissue could predict those men selected for active surveillance that would fail.[1] Currently, he is seeking a morphologic and molecular "signature" to separate less aggressive from more aggressive prostate cancer. Veltri has analyzed 80 cases of prostate cancer that were stratified by Gleason score and also biopsy samples from 70 men on active surveillance who turned out to have aggressive cancer, and from 70 men who had mild, slow-growing disease, and came up with a test.

"The results indicate we have developed an integrated, quantitative histomorphic and molecular biomarker-based predictor for the early detection of clinically more aggressive prostate cancer," he says. These preliminary results were reported by Dr. Guangjing Zhu, a post-doctoral fellow at the annual American Association for Cancer Research's annual meeting San Diego.

 
[1] Isharwal S, Makarov DV, Sokoll LJ, Landis P, Marlow C, Epstein JI, Partin AW, Carter HB, Veltri RW. ProPSA and diagnostic biopsy tissue DNA content combination improves accuracy to predict need for prostate cancer treatment among men enrolled in an active surveillance program. Urology. 2011 Mar;77(3):763.e1-6. doi: 10.1016/j.urology.2010.07.526. Epub 2011 Jan 8.