Am J Clin Pathol 2005;124:838-845
© American Society for Clinical Pathology
Anatomic Pathology / MESOTHELIN IN PANCREATICOBILIARY CARCINOMAS
Mesothelin Is Overexpressed in Pancreaticobiliary
Adenocarcinomas but Not in Normal Pancreas
and Chronic Pancreatitis
Raffit Hassan, MD,1Zoltan G. Laszik, MD, PhD,2Megan Lerner,3,4Mark Raffeld, MD,5
Russell Postier, MD,3and Daniel Brackett,3,4
Key Words: Mesothelin; Pancreatic, ampullar, and common bile duct cancer; Chronic pancreatitis; Immunohistochemistry
A b s t r a c t
Mesothelin, a cell surface glycoprotein present on
normal mesothelial cells, has been reported to be
expressed in pancreatic adenocarcinomas. We
conducted this study to fully characterize mesothelin
expression in surgically resected, formalin-fixed,
paraffin-embedded tissue specimens of 18 pancreatic
adenocarcinomas, 9 adenocarcinomas of the ampulla of
Vater, 12 adenocarcinomas of the common bile duct,
and 17 cases of chronic pancreatitis. Mesothelin
immunostaining was performed using the
antimesothelin monoclonal antibody 5B2. All 18 cases
(100%) of pancreatic adenocarcinomas showed
mesothelin expression, as did 8 (89%) of 9 cases of
ampullar adenocarcinoma and all 12 cases (100%) of
common bile duct adenocarcinoma. In all cases of
pancreaticobiliary adenocarcinoma, the adjacent
normal pancreas did not stain for mesothelin. Of 17
specimens of chronic pancreatitis, 16 were negative for
mesothelin expression, and 1 case showed weak
mesothelin staining of fewer than 5% of normal
pancreatic ducts. Our results demonstrated mesothelin
expression in the majority of pancreaticobiliary
adenocarcinomas and no expression in normal
pancreatic tissues and in chronic pancreatitis.
Pancreatic adenocarcinoma is the fourth leading cause of
cancer-related death for men and women in the United States,
with about an estimated 31,860 new cases diagnosed in 2004.1
The overall prognosis for patients with pancreatic cancer is
poor, with a median survival from diagnosis of 3 to 5 months,
a 12-month survival rate of approximately 10%, and a 5-year
survival rate of less than 5%.2,3Tumors arising from the distal
common bile duct (CBD) and ampulla of Vater are rare tumors
with clinical manifestations similar to those of pancreatic ade-
nocarcinoma but with a slightly better prognosis.4-8
Given the poor response of pancreatic adenocarcinoma to
standard chemotherapeutic agents, other strategies, including
immunotherapy, are being evaluated for the treatment of patients.
Immunotherapeutic approaches for the treatment of pancreatic
cancer include the identification and characterization of tumor
antigens, which could serve as targets for immunotherapy.9
Although pancreatic cancer–specific tumor markers are not avail-
able, several potential candidates have been identified by using the
serial analysis of gene expression (SAGE) technology.10By using
the online SAGE database (http://www.ncbi.nlm.gov/SAGE), the
tag for mesothelin was present consistently in pancreatic cancer
libraries but not in normal pancreas libraries.11
Mesothelin is a 40-kd glycosyl phosphatidylinositol–
linked cell surface glycoprotein that is present on normal
mesothelial cells lining the pleura, peritoneum, and pericardi-
um.12The mesothelin gene encodes a 69-kd precursor protein
that is processed to a 40-kd membrane-bound protein termed
mesothelin and a 31-kd shed fragment called megakaryocyte
potentiating factor. Mesothelin is the antigen recognized by mono-
clonal antibody (MAb) K1 that was generated by immunization
of BALB/c mice with the human ovarian carcinoma cell line
OVCAR-3.13Megakaryocyte potentiating factor was isolated
Am J Clin Pathol 2005;124:838-845 845
© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
attractive candidate for targeted therapy of pancreaticobil-
iary cancers given its high expression in these tumors and
absent expression in normal tissues except mesothelial
cells. Clinical trials of a recombinant immunotoxin target-
ing mesothelin are ongoing, as are experimental studies to
use mesothelin as a tumor vaccine.22
From the Laboratories of 1Molecular Biology and 5Pathology,
National Cancer Institute, National Institutes of Health, Bethesda,
MD; Departments of 2Pathology and 3Surgery, University of
Oklahoma Health Sciences Center, Oklahoma City; and 4Veterans
Affairs Medical Center, Oklahoma City.
Address reprint requests to Dr Hassan: Laboratory of
Molecular Biology, National Cancer Institute, National Institutes
of Health, 37 Convent Dr, Room 5116, Bethesda, MD 20892-4264.
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