A Novel Monoclonal Antibody, mAb Das-1, Identifies a Colonic Phenotype and Is Specific for Intraductal Papillary Mucinous Neoplasm (IPMN) with a High Risk for Malignant Transformation.
Koushik K Das, Gregor Krings, Martha B Pitman, Mari Mino-Kenudson. Massachusetts General Hospital, Boston
Background: IPMN is a precursor to pancreatic ductal adenocarcinoma, and consists of 4 epithelial subtypes with varying grades of dysplasia. Of those, the intestinal (IPMN-I) and gastric (IPMN-G) types comprise the vast majority of the neoplasms, and IPMN-G is known to have a much lower risk of developing invasive carcinoma than the other types. However, differentiation between subtypes remains a challenge, especially in the preoperative setting. mAb Das-1 is a murine monoclonal antibody that reacts specifically to a colonic epithelial phenotype. It is both sensitive and specific in identifying various pre-malignant and malignant lesions of the upper GI tract including Barrett's esophagus as well as incomplete gastrointestinal metaplasia associated with gastric cancer. The aim of this study was to assess the ability of mAb Das-1 to identify IPMNs associated with a high risk of malignant transformation.
Design: The study cohort consists of 94 distinct IPMN lesions and 13 IPMN-associated invasive carcinomas from 57 patients. A representative section from each lesion was stained with Das-1 by immunohistochemistry with appropriate controls. The cytoplasmic expression of Das-1 in greater than 5% of tumor cells was considered to be positive. Statistical significance was calculated by the Fisher exact test when compared to internal controls of normal pancreatic duct.
Results: Among IPMN-G, 0/14 (0%) lesions with low-grade dysplasia and only 2/20 (10%) with moderate dysplasia were reactive to Das-1. Compared to internal controls and IPMN-G with low-grade or moderate dysplasia, Das-1 expression was significantly higher in high-grade dysplasia (9/12 [75%], p<0.0005 and p<0.001, respectively). Among IPMN-I, 16/24 (67%, p<0.0001) lesions with moderate dysplasia were positive for Das-1 as were 16/18 (89%, p<0.0001) with high-grade dysplasia. Oncocytic-type IPMN demonstrated reactivity in 9/12 (75%, p<0.05). As for invasive IPMN, Das-1 was positive in 6/8 (75%, p<0.01) tubular adenocarcinomas and in 5/5 (100%, p<0.01) colloid carcinomas. The sensitivity and specificity of Das-1 in segregating high-risk/grade from low-risk lesions (IPMN-G with low-grade or moderate dysplasia) were 76% and 94%, respectively.
Conclusions: mAb Das-1 reacts with high specificity to high-risk/grade IPMN lesions compared to normal pancreatic ducts and low-risk lesions. The expression of this marker in preoperative samples such as cyst fluid may be useful as a tool to identify IPMN lesions at risk for malignant transformation.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 200, Tuesday Afternoon