Human pancreatic cancer fusion 2 (HPC2) 1-B3: a novel monoclonal antibody to screen for pancreatic ductal dysplasia.
BACKGROUND.: Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS.: Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS.: HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant (P = .002 by the Fisher exact test). CONCLUSIONS.: To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia.
Department of Pathology, Oregon Health and Science University, Portland, Oregon 97239, USA. morgante@ohsu.edu
Terry K
TK
Morgan
Karin
K
Hardiman
Christopher L
CL
Corless
Sandra L
SL
White
Robert
R
Bonnah
Henry
H
Van de Vrugt
Brett C
BC
Sheppard
Markus
M
Grompe
Ediz F
EF
Cosar
Philip R
PR
Streeter
D002288:Adenocarcinoma, Mucinous / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis*; D002471:Cell Transformation, Neoplastic; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000276:immunology*; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000175:diagnosis
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C421605:ELAC2 protein, human; D009363:Neoplasm Proteins