Discovery 
November 30, 2017

For today’s sophisticated pathology studies, it turns out that prostate tissue, like revenge, is better served cold. That’s because top pathologists like Angelo De Marzo, M.D., Ph.D., aren’t just looking at the cells anymore. They’re looking at the DNA and RNA – of cancer cells, and even of bacteria. It’s like the Dr. Seuss book, Horton Hears a Who: they keep looking at smaller and smaller things, and finding whole new worlds to study. The problem is, to gain the most information from these kinds of studies, the tissue needs to preserved, preferably by freezing it – which is easier said than done.

If you have ever had prostate tissue removed, it has gone right from the operating table to the pathology lab, where it was “fixed” in formalin, and then put it into a hard wax block. Then the pathologist made a few ultra-thin slices of tissue, stained with dye to make the cells easier to see, and put them on a microscope slide. The Gleason grade of cancer is based on how the prostate cells look.

But that’s just the tip of the iceberg these days: new technology allows scientists to look for mutations and gene activity. “The DNA and RNA in surgical specimens is a gold mine of new information,” says Patrick Walsh, M.D., University Distinguished Professor Emeritus, “and at Hopkins, where we have over 20,000 of them and longterm follow-up on our patients, there is much to learn.”

All that leftover tissue that becomes part of the permanent tissue database has traditionally been stored at room temperature – but De Marzo and colleagues have shown that this causes RNA and DNA to degrade over time. The ideal freezers “are large, commercial, ultra-low temperature units that cost a lot of money and take up a lot of space,” says De Marzo.

Recently, Javier Baena, M.D., and Qizhi Zheng M.D. from De Marzo’s lab, along with Brady colleagues Karen Sfanos, Ph.D., and Bruce Trock, Ph.D., and Eva Corey M.D., and Colm Morrissey Ph.D., from the University of Washington, found that at room temperature, “most genes showed markedly diminished signals by five years, with significant degradation beginning at one year.” Fortunately, Baena, Zheng, and Sfanos found that if new slides are stored in an inexpensive household freezer, the RNA signals will be preserved, at least up to five years.

“Our findings strongly suggest that the standard method of room temperature storage should be called into question and changed,” says De Marzo. Clearly, pathology labs don’t have the money or space to store all prostate tissue specimens in freezers. But they could use smarter storage of the most critical blocks of tissue – probably only one or two for each patient.

This work was supported by The U.S. Department of Defense Prostate Cancer Biorepository Network (PCBN), and the National Cancer Institute. Other investigators who took part in the study are Helen Fedor B.S., and Jessica Hicks M.Sc., from Johns Hopkins, and Toby Cornish M.D., Ph D., from the University of Colorado.