DOG1 Antibody in the Differential Diagnosis of Gastrointestinal Stromal Tumors A Study of 1840 Cases

被引:322
作者
Miettinen, Markku [1 ]
Wang, Zeng-Feng [2 ]
Lasota, Jerzy [1 ]
机构
[1] Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USA
[2] Armed Forces Inst Pathol, Sci Labs, Washington, DC 20306 USA
关键词
DOG1; gastrointestinal stromal tumor; sarcoma; KIT; PDGFRA; mutation; chloride channel protein; TERM-FOLLOW-UP; KINASE-C-THETA; PDGFRA MUTATIONS; MONOCLONAL-ANTIBODY; GASTRIC TUMORS; PKC-THETA; KIT; MARKER; EXPRESSION; MORPHOLOGY;
D O I
10.1097/PAS.0b013e3181a90e1a
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Gastrointestinal stromal tumors (GISTs), KIT or platelet derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors of the gastrointestinal (GI)-tract and abdomen, require a precise diagnosis so that the patients may benefit from the newly introduced tyrosine kinase inhibitor drugs. The limitations of the current main tools, KIT immunohistochemistry and KIT/PDGFRA mutation analysis, include lack of KIT expression and Mutations ill some GISTs. Ill this study we examined 1168 GISTs of different sites and histologic subtypes, and 672 other tumors and normal tissues for discovered oil GIST-1 (DOG1) clone K9, a newly introduced immunohistochemical marker, a chloride channel protein. All GISTs and selected non-GISTs were independently evaluated for KIT. In the GI tract, Cajal cells and gastric surface epithelia were DOG1-positive. The overall sensitivity of DOG1 and KIT in GISTs was nearly identical: 94.4% and 94.7% and results in GISTs were generally concordant. Gastric spindle cell GISTs was nearly uniformly positive for both markers, whereas DOG1 performed slightly better in gastric epithelioid GISTs that included PDGFRA mutant GISTs. In the intestinal GISTs, KIT was slightly more sensitive than DOG1. Negativity for both DOG1 and KIT was observed in 2.6% of GISTs of GI tract. KIT or PDGFRA mutations were detected in 11/24 DOG1-negative GISTs Supporting the diagnosis of GIST. DOG1 expression was also generally present in extragastrointestinal and metastatic GISTs. DOG I was highly specific for GIST, but exceptional DOG1-positive other mesenchymal tumors included uterine type retroperitoneal leiomyomas, peritoneal leiomyomatosis, and synovial sarcomas (positive in 5/41 4/17, and 6/37 cases). Leiomyomas colonized by DOG1-positive Cajal cells should not be confused with GISTs. DOG1 positivity was relatively common in esophageal squamous Cell and gastric carcinomas, whereas it was rare in colorectal carcinomas. DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and Specificity Should be recognized.
引用
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页码:1401 / 1408
页数:8
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