DOG-1 Expression in Non-Gastrointestinal Stromal Tumor (GIST) Neoplasms.
Jessica Hemminger, Joel Mayerson, William Kraybill, Thomas Scharschmidt, Hans Iwenofu. The Ohio State University Medical Center, Columbus
Background: Accurate and practical diagnosis of gastrointestinal stromal tumors (GISTs) is of great importance given the therapeutic benefit of KIT and PDGFRA tyrosine kinase inhibitors. Recently, a transmembrane calcium-regulated chloride channel protein, discovered on GIST-1 (DOG1), has been shown to be sensitive and specific for GISTs. Thus far, studies of the commercially available DOG1 antibody clone K9 (Novocastra) have primarily focused on spindled cell neoplasms in the differential diagnosis of GISTs. Here, we further characterize DOG1 by studying immunohistochemical (IHC) staining patterns in a range of mesenchymal and epithelial tumors.
Design: A formalin-fixed paraffin-embedded block was obtained for each of the following tumors (n=155): GISTs, epithelioid (n=10) and spindled (n=10) types; melanoma, epithelioid (n=10) and spindled/desmoplastic (n=9) types; schwannoma (n=10); neurofibroma (n=10); leiomyosarcoma (n=10); low grade fibromyxoid sarcoma (n=5); angiosarcoma, epithelioid (n=3), spindled (n=5), and mixed (n=2) types; epithelioid sarcoma (n=5); clear cell sarcoma (n=3); synovial sarcoma (n=10); malignant peripheral nerve sheath tumor, epithelioid (n=1) and spindled (n=10) types; alveolar soft part sarcoma (n=3); chordoma (n=5); pleomorphic undifferentiated sarcoma (n=5); perineurioma (n=4); adenocarcinoma, lung (n=5), colon (n=5), endometrial (n=5); renal cell carcinoma, clear cell (n=5) and chromophobe (n=5) types. Utilizing standard IHC staining protocols, full sections were stained with DOG1 antibody clone K9. Staining was assessed for intensity (1-3+), percentage of tumor positivity, and location.
Results: Of the 20 GISTs, 95% (19/20) expressed DOG1. Over half (11/20) were diffusely positive (>95%) with moderate to strong intensity (2-3+). Evaluation of epithelial neoplasms, revealed focal staining of colorectal (2/5) and endometrial (2/5) adenocarcinomas of 2+ intensity with the percentage of tumor cells ranging from <5 to 40%. DOG1 stained the luminal aspects, and, in one colorectal tumor, staining was cytoplasmic and membranous. One case of schwannoma showed focal (5%) staining of 2+ intensity. The remainder of the neoplasms did not express DOG1.
Conclusions: Our study supports that DOG1 is a highly sensitive and specific marker for GISTs. Herein, we also describe DOG1 positivity in colorectal and endometrial adenocarcinomas with prominent luminal pattern as well as an instance of focal expression in a schwannoma. Given the novelty of DOG1, the staining patterns of these non-GIST neoplasms require further characterization in a large cohort study.
Category: Bone & Soft Tissue
Monday, February 28, 2011 1:00 PM
Poster Session II # 2, Monday Afternoon