|
A
novel monoclonal antibody against DOG1 is a sensitive and specific
marker for
gastrointestinal stromal tumors.
Am J Surg Pathol.
2008 Feb; 32(2): 210-8.
Espinosa,
Inigo MD1; Lee, Cheng-Han MD, PhD1;
Kim, Mi Kyung MD, PhD1;
Rouse, Bich-Tien MS1; Subramanian, Subbaya PhD1;
Montgomery, Kelli BA1; Varma, Sushama MS1;
Corless,
Christopher L. MD, PhD3; Heinrich, Michael C. MD3;
Smith,
Kevin S. PhD1; Wang, Zhong PhD1;
Rubin, Brian MD, PhD4;
Nielsen, Torsten O. MD, PhD5; Seitz, Robert S. MD2;
Ross,
Douglas T. MD, PhD2; West, Robert B. MD, PhD1;
Cleary,
Michael L. MD1; van de Rijn, Matt MD, PhD1
1Department of
Pathology, Stanford University Medical Center,
Stanford
2Applied
Genomics Inc, Burlingame, CA
3Department of
Pathology and OHSU
Cancer Institute, Oregon
Health and Science
University,
Portland, OR
4Departments of
Anatomic Pathology
and Molecular Genetics, Lerner Research Institute and Taussig
Cancer
Center,
Cleveland
Clinic, Cleveland,
OH
5Department of
Pathology, University
of British Columbia,
Vancouver, Canada
Abstract
Gastrointestinal
stromal tumors
(GIST) occur primarily in the wall of the intestine and are
characterized by
activating mutations in the receptor tyrosine kinases genes KIT or
PDGFRA. The
diagnosis of GIST relies heavily on the demonstration of KIT/CD117
protein
expression by immunohistochemistry. However, KIT expression is absent
in
approximately 4% to 15% of GIST and this can complicate the diagnosis
of GIST in
patients who may benefit from treatment with receptor tyrosine kinase
inhibitors. We previously identified DOG1/TMEM16A as a novel marker for
GIST
using a conventional rabbit antipeptide antiserum and an in situ
hybridization
probe. Here, we describe 2 new monoclonal antibodies against DOG1
(DOG1.1 and
DOG1.3) and compare their staining profiles with KIT and CD34
antibodies on 447
cases of GIST. These included 306 cases with known mutational status
for KIT
and PDGFRA from a molecular consultation service. In addition, 935
other
mesenchymal tumors and 432 nonsarcomatous tumors were studied. Both
DOG1
antibodies showed high sensitivity and specificity for GIST, with
DOG1.1
showing some advantages. This antibody yielded positive staining in 370
of 425
(87%) scorable GIST, whereas CD117 was positive in 317 of 428 (74%)
GIST and
CD34 in 254 of 430 (59%) GIST. In GIST with mutations in PDGFRA, 79%
(23/29)
showed DOG1.1 immunoreactivity while only 9% (3/32) and 27% (9/33)
stained for
CD117 and CD34, respectively. Only 1 of 326 (0.3%) leiomyosarcomas and
1 of 39
(2.5%) synovial sarcomas among the 935 soft tissue tumors examined
showed
positive immunostaining for DOG1.1. In addition, DOG1.1
immunoreactivity was
seen in fewer cases of carcinoma, melanoma, and seminoma as compared
with KIT.
 |
 |
| |
(website link- subscription required) |
|
