Study Finds Precancerous Pancreatic Lesions More Widespread Than Expected

The researchers are interested in understanding why some lesions turn into pancreatic cancer to better identify those with a high risk of the disease. 

A surprisingly large number of healthy people may be walking around with precancerous lesions in the pancreas, judging from a study published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).

More than half of the healthy pancreases analyzed in the study were found to have pancreatic intraepithelial neoplasia, or PanIN, lesions, which have long been considered a precursor to pancreatic cancer. The lesions were found in individuals as young as 20 years old and in various racial/ethnic groups and had some traits previously detected in cancer cells.

“By analyzing true normal [pancreases], we found that PanINs were commonly found in individuals of diverse age and race, and may have already acquired some features of malignant cells,” said lead author Eileen Carpenter, MD, PhD, a researcher and physician at the Rogel Cancer Center and Michigan University at the University of Michigan. “Given that pancreatic cancer is exceedingly rare, the widespread occurrence of PanINs in individuals of various age and race challenges the paradigm that PanINs always evolve into cancer.”

Marina Pasca di Magliano, PhD

“Understanding why some PanINs evolve to cancer and others do not will be important to accurately predict who is at risk of pancreatic cancer and to develop techniques for cancer interception,” said Marina Pasca di Magliano, PhD, senior author of the study and a researcher at the Rogel Cancer Center and Michigan Medicine at the University of Michigan. “The composition of the microenvironments surrounding PanINs might be a key factor.”

Pancreatic cancer is a rare but highly fatal disease, with a five-year relative survival rate of 11.5%. With few early symptoms, it is typically diagnosed at advanced stages when it is more difficult to treat. 

The larger purpose of the study was to trace the transition of pancreatic tissue from the normal, healthy state, through a precancerous condition, to cancer. 

“Understanding how pancreatic tissue evolves as it transitions from normal to precancerous to cancerous will be key to identifying strategies for early detection, prevention, and treatment of pancreatic cancer,” Pasca de Magliano said. “Unfortunately, it has been difficult to understand the baseline characteristics of the pancreas due to a lack of normal pancreatic tissue available for research.”

To characterize normal pancreatic tissue, researchers partnered with Gift of Life Michigan, an organ donor registry, to obtain healthy pancreases from 30 recently deceased donors for whom no suitable transplant recipients were identified. Because the pancreases were donated following brain death, blood flow was maintained until the organ could be removed and immediately cooled, which helped preserve the tissue for scientific analyses.

Donors were between 20 and 70 years old at the time of death and did not have any pancreatic diseases. There were 20 male and 10 female donors. Approximately two-thirds of donors were white, approximately one-third were African American, one donor was Asian, and one donor was of unknown race. 

By analyzing tissue collected from various regions of the pancreas, the researchers discovered PanINs in 18 of the 30 donor pancreases, representing all age and racial groups. The PanINs identified in the study had features of both healthy and cancerous pancreatic cells.