Pathologist Angelo M. DeMarzo, M.D., Ph.D., the Dr. and Mrs. Peter S. Bing Scholar, is looking ahead — to a point where he is one or two steps ahead of prostate cancer — and hoping to change the future. In remarkable studies of prostate tissue samples, reported in previous editions of Discovery, he has found the equivalent of the chaos that astronomers see in star-forming regions of galaxies. It’s a crazy, ever-changing mix of cells called PIA — proliferative inflammatory atrophy. Some of these cells seem to be dying, but are actually undergoing rapid-fire change. DeMarzo believes that PIA is the result of two main problems — a bad diet, which causes oxidative damage, and inflammation within the prostate — and that these PIA lesions are "on their way towards cancer."

But he needs definitive proof that PIA is cancer in progress. Imagine you took a series of snapshots of a building going to ruin. Long before part of the roof falls in, some shingles blow off. A window cracks. Rain gets in. This is the kind of evidence DeMarzo is looking for, on a very tiny scale — intermediate changes in DNA between normal cells and cancer cells. The most common of these are altered clumps called "hypermethylated CpG islands" in a gene called GSTPi, which is disabled early on in prostate cancer. With GSTPi, a protective gene, out of the way, cancer develops much more easily. "We believe that PIA will contain intermediate levels of CpG island methylation," says DeMarzo, "greater than normal, but less than cancer."

Ultimately, their hope is to spot
precancerous cells at such an
early stage that they can reverse
the damage—fix the shingles, in
effect, and keep out the rain.

He and colleagues are working to correlate the number of altered CpG islands with the type of atrophy, the extent and pattern of acute and chronic inflammation, and the presence of nearby cancer. They’ll also be looking for other DNA abnormalities in PIA cells, searching for methylation changes in other genes that are known to be mutated in prostate cancer. Ultimately, their hope is to spot precancerous cells at such an early stage that they can reverse the damage — fix the shingles, in effect, and keep out the rain.