title: mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN).
abstract: OBJECTIVE
  Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation.
  
  
  METHODS
  mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot.
  
  
  RESULTS
  Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p<0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively.
  
  
  CONCLUSIONS
  mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification.
authors.affiliation: Department of Internal Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Koushik K
authors.initials: KK
authors.lastname: Das
authors.affiliation: Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Del-Castillo
authors.affiliation: Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Morales-Oyarvide
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ebubekir
authors.initials: E
authors.lastname: Daglilar
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Forcione
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Brenna C
authors.initials: BC
authors.lastname: Bounds
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Brugge
authors.affiliation: Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Martha B
authors.initials: MB
authors.lastname: Pitman
authors.affiliation: Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Kiron M
authors.initials: KM
authors.lastname: Das
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000276:immunology; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000276:immunology*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000276:immunology; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000276:immunology
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; C467479:DAS-1 protein, human
keywords: Pancreatic Cancer; Pancreatic Pathology; Pancreatic Tumours