Discovery
January 01, 2017

If you’ve ever had a prostate biopsy, you may have encountered the words, “isolated high-grade PIN.” PIN stands for “prostatic intraepithelial neoplasia,” and if you have it, you’re not alone: an estimated 50,000 to 70,000 men are told that their biopsy shows this finding. Now, what is it? That’s a good question, and the answer has just changed. “For many years, we thought high-grade PIN represented a precursor of prostate cancer,” says William G. Nelson, M.D., Ph.D., the Marion I. Knott Director and Professor of Oncology and Director of the Sidney Kimmel Comprehensive Cancer Center. “Thus, a diagnosis of high-grade PIN was unsettling for both the patient and the physician.” Just to make sure cancer wasn’t there, “often men with high-grade PIN were subjected to a second biopsy, and some of the men were indeed found to have cancer.”

Because nobody really knew what PIN was, and with the hope that it might be reversible, over the last decade several clinical trials were undertaken to see “whether PIN could be intercepted and prevented from progressing to cancer.” Scientists, including Nelson, studied many promising foods and vitamins that are in foods, like “green tea catechins, lycopene from tomatoes and other fruits and vegetables, selenium, vitamins, hormones, and drugs,” Nelson adds. “Unfortunately none of the trials succeeded: the numbers of men ultimately found to have prostate cancer were unaffected by any intervention.”

New research sheds light on why some of these men turned out to have cancer: most likely, it was already there, and as urologist Patrick C. Walsh, M.D., says, although it may be possible to delay or slow growth, once cancer is present “you can’t unring the bell.” In studies published in the Journal of Pathology and Cancer Prevention Research, scientists Michael Haffner, M.D., Angelo De Marzo, M.D., Ph.D., Nelson, and colleagues have suggested — using new technologies that allowed them to look at the DNA of PIN and prostate cancer — that many areas of high-grade PIN are not cancer precursers at all. “Rather,” Nelson explains, “these PIN lesions actually reflect the growth of established cancer into prostate ducts. This may explain why some men with isolated high-grade PIN prove to have cancer on a subsequent biopsy,” and why, so far, no dietary agents have proven successful at preventing cancer in clinical trials.

“Going forward, we hope to be able to figure out which PIN lesions are actually cancer, and which are just precursors but not yet cancer,” says Nelson. “Of course, cancer growing in ducts should be treated like cancer, and with what we know now, cancer precursors require no immediate treatment. In the future, with a better sense of which men have PIN only, we may revisit clinical trials of agents that might prevent PIN from ever becoming cancer.”