Human aspartyl (asparaginyl) beta-hydroxylase monoclonal antibodies: potential biomarkers for pancreatic carcinoma.

Abstract

Pancreatic adenocarcinoma is among the top 10 leading causes of death due to cancer in the United States. The lack of reliable and sensitive biomarkers for this disease makes it difficult to render an early diagnosis. To evaluate carcinoma-associated monoclonal antibodies (MoAbs), including AF-20, SF-25, and FB-50, for their binding specificity to pancreatic adenocarcinoma relative to normal pancreatic tissue. In addition, binding of the Th9 MoAb to human Reg 1 protein was studied because of its potential role in cell growth. Adjacent histologic sections were immunostained with each of the MoAbs and graded on a scale of 0 to 4+, corresponding to the relative distribution and intensity of immunoreactivity within the tumor and normal adjacent tissue. Intense levels (grade 3 or 4) of FB50 immunoreactivity were detected in 19 of 19 tumors but not in normal adjacent pancreatic tissue. In addition, increased levels of FB50 immunoreactivity were detected in at least 75% of the tumor cells in 18 of the 19 cases. SF-25 immunoreactivity similarly distinguished pancreatic adenocarcinoma from normal pancreas in 14 of 19 cases. In contrast, AF20 immunoreactivity was detected in 6 of 19 pancreatic adenocarcinomas, and for the most part, the labeling was focal and of a low level. TH9 immunoreactivity was detected in 5 of 19 tumors but also in normal as well as inflamed adjacent pancreatic tissue. These results suggest that the FB50 and SF25 MoAbs represent excellent potential biomarkers of pancreatic adenocarcinoma and could be configured in an immunoassay for detecting pancreatic adenocarcinoma cells in biologic fluids.