High-Grade PIN: Wolf in Sheep's Clothing?

Published in Discovery - Winter 2016

PIN, short for "prostatic intraepithelial neoplasm" is a condition in prostate biopsy tissue that pathologists see under the microscope. The cells are funny-looking; pathologists consider them not to be cancerous, but not normal-looking, either, and for years, PIN has been considered a sort of precursor for prostate cancer.

"Although PIN shares many hallmarks of prostate cancer, it does not appear to invade the surrounding normal tissue," says molecular pathologist Michael Haffner, M.D. "When PIN cells are found in isolation, and no actual cancer cells are found, it's not always clear what to make of the finding. "As a matter of precaution, urologists usually recommend repeat biopsies if there are many cores of tissue with this finding to make sure that everything's okay – that the PIN itself is not progressing to become cancer, or that cancer cells were not missed the first time around. But new findings by Haffner, molecular pathologist Angelo De Marzo, genomics expert Srinivasan Yegnasubramanian and oncologist Bill Nelson may call for extra precaution in some men. By way of a series of genetic analyses, they were able to trace the evolutionary ancestry — to look back in time, in effect — of PIN lesions in prostate tissue specimens. "Surprisingly, we found that many lesions that look like a precursor lesion have identical genetic fingerprints of invasive cancer cells," says Haffner. "Therefore, at least a subset of PIN lesion likely represents cancer cells that have invaded into normal prostate glands — a potentially dangerous 'wolf in sheep's clothing.' This study provides important new insights into how prostate cancer cells can grow and spread, but also establishes new molecular markers that can be used as helpful tools in the future to discriminate less harmful precursor lesions from invasive cancers."

Urologist Patrick C. Walsh, M.D., reassures men who have PIN that it is most likely just that — precursor cells that are not cancer. "But if it is high-grade PIN that is found in multiple cores or is bilateral (in tissue from both sides of the prostate), then a repeat biopsy is recommended."