Monoclonal Antibody DOG1.1 Shows Higher Sensitivity Than KIT in the Diagnosis of Gastrointestinal Stromal Tumors, Including Unusual Subtypes

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Approximately 85% of GISTs harbor activating mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) gene and approximately 95% of GISTs are positive for KIT (CD117) by immunohistochemistry. Nevertheless, approximately 5% of GISTs lack KIT expression. Inhibition of KIT and PDGFRA by tyrosine kinase inhibitors has revolutionized the treatment of GISTs and demands accurate tumor classification. DOG1.1 is a recently described mouse monoclonal antibody reported to have superior sensitivity and specificity compared with KIT (CD117) and CD34. We evaluated this new antibody on a group of 81 GISTs obtained from 74 patients with special regard to KIT-negative GISTs (n=28), pediatric GISTs (n=11), and GISTs associated with neurofibromatosis type I (NF1) (n=16). Conventional GISTs (n=26) were also included. All conventional KIT-positive GISTs, all NF1-associated GISTs, and 9/11 pediatric GISTs expressed DOG1.1. DOG1.1 was expressed in 10/28 (36%) of KIT-negative tumors. The staining pattern was cytoplasmic and/or membranous. This study demonstrates that DOG1.1 is a sensitive immunohistochemical marker for GIST, comparable with KIT, with the additional benefit of detecting 36% of KIT-negative GISTs. DOG1.1 is also a sensitive marker for unusual GIST subgroups lacking KIT or PDGFRA mutations. In tumors that are negative for both KIT and DOG1.1, mutational screening may be required to confirm the diagnosis of GIST.

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

“…When mutation analysis had not previously been performed, genomic DNA was extracted from the paraffinembedded tumor, and exons 9, 11, 13, and 17 of KIT and exons 12 and 18 of PDGFRA were sequenced as previously described (6). Additional tumor samples, not from participants in the NIH Pediatric and WT GIST Clinic used in this study, have been described previously (4,35,36). Ten additional pediatric GIST cases were collected from the archives and referral cases of one of the authors (M.O.)…”

Cytogenetic and immunohistochemical characterization of mammary analogue secretory carcinoma of salivary glands

“…It was first described as a calcium-activated chloride channel in 2008 and is routinely used in the diagnosis of gastrointestinal stromal tumours (GIST) [10][11][12][13][14][15][16]. Its expression pattern in salivary gland neoplasms is not well established although a recent study showed expression in acinar lumens in both normal glands and ACC [13].…”

Gastrointestinal tract spindle cell lesions—just like real estate, it's all about location

“…DOG1 (discovered on GISTs1) is another antibody that was discovered using gene expression profiling and is also expressed by most GISTs; it can be a supplement to KIT/CD117 labeling. [55][56][57] However, an important pitfall is that nearly a third of gastric adenocarcinomas express DOG1 55 (Figures 9c-e), an issue with epithelioid GIST (Figure 9f) but one usually resolved by noting strong diffuse keratin expression in carcinomas. Another pitfall is that epithelioid GISTs sometimes label with melan-A.…”