2014 PCRP Investigator Vignette

Title: Evaluating Novel Predictors of Risk for Aggressive Prostate Cancer

Investigator: Elizabeth Platz, ScD; Johns Hopkins University

We have two DoD grants currently, which is very exciting to us. So, the first one is a Population Science Award, and, in that award, we are studying whether inflammation in the prostate, which is a follow-on from our original work, so looking actually in prostate tissue, whether inflammation can tell us about the risk of the disease in the future and risk of poor outcome in men in the future.

So, we are studying two groups of men. So, the first one is a group at Johns Hopkins; again, these are men who were diagnosed with prostate cancer. They were surgically treated. We look in their tissue, the tissue that was removed at surgery, for the presence of inflammation. So inflammation is certain types of immune cells that move into prostate tissue. There are different kinds of immune cells that are present, so we'll assess the type as well, and then we'll relate that to the risk of recurrence in the future. The second study, which is within that same DoD application, we're looking at the risk of prostate cancer. In that study, we're taking two resources: one is the Prostate Cancer Prevention Trial, and the second is the SELECT Trial. They're both conducted by SWOG, the Southwest Oncology Group, and, in the first study, the men who were enrolled, if they were not diagnosed with prostate cancer during the trial, they were biopsied at the end. And some of those men enrolled in the second trial, SELECT, and so what we're doing is, we're using the tissue from the end of the first trial to be the baseline biopsy for the men in the second trial. So we'll be able to look at the time before they develop prostate cancer and whether inflammation tells us about their future risk of the disease. That's very exciting to us; no one has been able to study inflammation prospectively in men without an indication for biopsy. So this is very, very exciting work for us.

This work is a multidisciplinary study, so we're collaborating with Angelo DeMarzo, longtime collaborator of mine. We've done a number of studies together. He's a genital-urinary pathologist and was a big part of the DoD Integration Panel for many years. The other collaborators that we have on this project are from the stat center from SWOG.

We are in year 2 of the work, so we have the tissue. It's been sectioned and has been stained, so we are at the point of evaluating how much inflammation is present and evaluating the nature of the inflammatory cells that are present in the tissue.

The second DoD grant that I ever had was to investigate the role of telomere length in the risk of poor outcome and then with prostate cancer. Tumors tend to have shorter telomeres than normal cells, and I thought there must be information here, there must be information about how aggressive the disease is based on how short the telomeres are. So that was our original hypothesis going in: is the shorter the telomeres in the cancer, the higher the risk of more aggressive disease. But that's not what we found. Uniformly, these tumors have shorter telomeres. What we found instead was that it was the variability in telomere length from cell to cell that provided information about risk of death from prostate cancer in men who had clinically organ-confined disease and who were surgically treated. And that biomarker was particularly informative when we combined it with length of the telomeres in the nearby stromal cells. So, men who had more-variable telomere length from cell to cell in their prostate cancer combined with short telomeres in the stromal cells that were nearby had 14 times the risk of dying of their prostate cancer, even though they had been surgically treated. So we think this is a really important finding, and that led to the next DoD grant, to follow up on that prior DoD work, and we are studying again telomere length, variability in length in the cancer, short telomeres in the stromal in relation to poor outcome. So we are using technology to speed up the assessment of telomere length and then we're also going to try to optimize the cut points, so that we'll be able to better say what-what would be the particular extent of variability, the particular shortness of the telomeres that is most prognostic. Our goal is some day to have a clinical test that could be applied for men at the time of surgery to know about their risk of poor outcome, because perhaps those men could be followed more closely, greater surveillance, maybe they would need adjuvant therapy, or perhaps even the opposite could be true. Perhaps telomere length, variability in length, would tell us so much about the nature of how aggressive the disease is. Perhaps the man would not have aggressive disease at all and would not need additional treatment and he could just go on and live his life. So, that's what we're hopeful for.