mAb Das-1 identifies pancreatic ductal adenocarcinoma and high-grade pancreatic intraepithelial neoplasia with high accuracy

Abstract

Pancreatic intraepithelial neoplasia (PanIN) is a microscopic precursor lesion to pancreatic ductal adenocarcinoma (PDAC); however, there are few biomarkers that segregate high-grade PanIN/PDAC from low-grade PanIN lesions. mAb Das-1 is a monoclonal antibody against a colonic epithelial antigen that is reactive to premalignant conditions of the upper gastrointestinal tract including Barrett's esophagus, incomplete-type gastric intestinal metaplasia, and intraductal papillary mucinous neoplasm of the pancreas at high risk of malignancy. We sought to examine a role for Das-1 expression in differentiating high-grade PanIN/PDAC from low-grade PanIN lesions. We examined surgical specimens from 86 patients and 2 autopsied pancreata (74 with and 14 without PDAC) with 107 distinct PanIN lesions, 74 PDAC cases, and 32 associated lymph node metastases, with internal controls of normal pancreatic ducts observed in 56 cases. All of the normal pancreatic duct controls (0/56) and low-grade PanIN (0/95) lesions were nonreactive to Das-1. Das-1 expression among high-grade PanIN (7/12, 58%), PDAC (55/74, 74%), and lymph node metastasis (21/32, 66%) cases was significantly higher (p < 0.0001). Clinicopathologically, Das-1 reactivity was significantly correlated with nodal metastasis (p = 0.021). Overall, the sensitivity, specificity, and accuracy of Das-1 in segregating high-grade PanIN/PDAC from low-grade PanIN lesions and normal ducts were 72%, 100%, and 90%, respectively. Thus, mAb Das-1 reacts with high specificity with high-grade PanIN and PDAC and may help in preoperative diagnosis and/or clinical risk stratification.

Keywords: Biomarker; CEP; Pancreatic adenocarcinoma; Pancreatic intraepithelial neoplasia (PanIN); mAb Das-1.

Figure 1:

Normal colonic mucosa exhibits cytoplasmic expression of Das-1 (A), while normal small intestinal mucosa is negative for Das-1 (B). Similarly, normal pancreatic parenchyma including pancreatic ducts are non-reactive to Das-1 (C: H&E stain, D: Das-1 immunohistochemistry). Interestingly, rare small foci with acinar to ductal metaplasia in the setting of chronic pancreatitis secondary to pancreatic ductal adenocarcinoma shows strong membranous and/or cytoplasmic Das-1 expression (E: H&E stain, F: Das-1 immunohistochemistry).

Figure 2:

Low-grade PanIN (PanIN-1 and PanIN-2) are non-reactive to Das-1 (A: H&E stain, B: Das-1 immunohistochemistry), while cytoplasmic and/or membranous patterns of Das-1 expression is seen in the majority of high-grade PanIN (PanIN-3) lesions (C: H&E stain, D: Das-1 immunohistochemistry).

Figure 3:

Examples of pancreatic ductal adenocarcinomas with grade 1 (A & B), grade 2 (C) and grade 3 (D) Das-1 expression (A, C & D: Das-1 immunohistochemistry, B: H&E stain).

Figure 4:

A) Das-1 staining highlighting perineural invasion. B) A malignant duct in the vicinity of neural tissue is positive for Das-1 (arrow heads; an area marked by a rectangle is magnified in the right-side image), while normal interlobular duct and low-grade PanIN lesions are non-reactive to Das-1 (arrows). C) Lymphatic invasion with Das-1 expression. D) An example of lymph node metastasis with grade 3 Das-1 expression (an area marked by a rectangle is magnified in the right-side image).