title: The novel monoclonal antibody HPC2 and N-cadherin distinguish pancreatic ductal adenocarcinoma from cholangiocarcinoma.
abstract: Metastatic pancreatic ductal adenocarcinoma and primary cholangiocarcinoma are morphologically very similar and, therefore, challenging to distinguish in liver biopsies. The distinction is important because surgical management and prognosis differ significantly. Several immunohistochemical markers have been evaluated to aid this diagnosis, but aside from N-cadherin, which labels cholangiocarcinoma, few provide the combination of good sensitivity and specificity. Our laboratory recently developed the novel monoclonal antibody human pancreatic cancer fusion #2 (HPC2) that recognizes pancreatic cancer. We hypothesized that the combination of our new marker and N-cadherin can assist in distinguishing metastatic pancreatic cancer from cholangiocarcinoma. We immunostained resections of 60 pancreatic ductal adenocarcinomas and 31 cholangiocarcinomas for the HPC2 and N-cadherin antigens. We also stained 24 gallbladder adenocarcinomas, 11 ampullary adenocarcinomas, and 10 metastatic colonic adenocarcinomas to the liver. Sections were independently scored by 2 pathologists with good agreement using both markers (κ statistics, 0.62-0.64; P < .0001). HPC2 was observed in 80% of pancreatic cancers (48/60), 82% of ampullary (9/11), and 32% (10/31) of cholangiocarcinomas. N-cadherin stained 27% (16/60) of the pancreas cases and 58% (18/31) of the cholangiocarcinomas. Gallbladder and colon cancers were usually double negative (18/24 and 8/10, respectively). Each marker provided significant likelihood ratios to separate pancreatic cancer (HPC2, 2.48 [1.46-4.19]; P < .0001) from cholangiocarcinoma (N-cadherin, 2.17 [1.3-3.64]; P < .01). The combination of both markers provided even better specificity and positive likelihood ratios. We conclude that HPC2 and N-cadherin significantly improve accurate classification of pancreatic cancer and cholangiocarcinoma.
authors.affiliation: Department of Pathology, Oregon Health and Science University, Portland, OR 97239, USA. hooperj@ohsu.edu
authors.forename: Jody E
authors.initials: JE
authors.lastname: Hooper
authors.forename: Terry K
authors.initials: TK
authors.lastname: Morgan
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Brett C
authors.initials: BC
authors.lastname: Sheppard
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Philip R
authors.initials: PR
authors.lastname: Streeter
mesh_terms: D000911:Antibodies, Monoclonal; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D015820:Cadherins; C421605:ELAC2 protein, human; D009363:Neoplasm Proteins