Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: Evidence for multistep carcinogenesis

The pathobiology of precursor lesions leading to invasive pancreatic adenoc arcinoma remains a controversial area, but knowledge of the mechanisms of t umorigenesis may lead to possibly earlier detection, prevention, and treatm ent in the future. We hypothesize that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions and ate part of a continuous devel opmental spectrum evolving into ductal adenocarcinoma of the pancreas. To f urther define this sequence, we studied the immunohistochemical markers HER -2/neu, K-ras, and p53 in 15 adenocarcinomas and 15 nonmalignant specimens of the pancreas. The 15 nonmalignant specimens of the pancreas included bot h normal pancreas and chronic pancreatitis. Overall, HER-2/neu was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 o f 30, 11 of 20 (55%), 10 of 15 (67%), and 12 of 15 (80%), respectively, wit h progressive increase in the intensity of staining; p53 was positive in 1 of 30 (3%), 0 of 20, 3 of 15 (20%), and 13 of 15 (80%), respectively, and K -ras was positive in 1 of 30 (3%), 6 of 20 (30%), 11 of 15 (73%), and 8 of 15% (53%), respectively. These data support the hypothesis that ductal hype rplasia and dysplasia of the pancreas represent precursor lesions, and, in a fashion similar to that in colorectal tumorigenesis, pancreatic cancer se ems to accumulate progressive genetic alterations. HUM PATHOL 30:123-129. C opyright (C) 1999 by W.B. Saunders Company.