CD117: A sensitive marker for gastrointestinal stromal tumors that is more specific than CD34

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the GI tract. These tumors are both phenotypically and genotypically different from true leiomyomas and usually express CD34, a hematopoietic progenitor cell antigen. CD34, however, is also present in a wide variety of fibroblastic and endothelial cell tumors. In this immunohistochemical study of CD117, we evaluated 85 cases of GIST and more than 150 other mesenchymal tumors, including leiomyomas and schwannomas. CD117, the c-kit proto-oncogene product, is expressed in subsets of hematopoietic stem cells, mast cells, melanocytes, and interstitial cells of Cajal of the GI tract. CD117 was almost always (85%) expressed in both benign and malignant GISTs. CD117 was observed both in the spindle cell and epithelioid subtypes of GISTs in all locations. In addition to reacting with the CD34-positive GISTs, CD117 was positive in some CD34-negative cases. Approximately one-third of GISTs coexpressed CD117 and smooth muscle actins. In contrast, true leiomyomas (desmin and actin-positive) and schwannomas in both GI and peripheral locations were consistently negative for CD117. Solitary fibrous tumors and Kaposi's sarcomas, which are typically CD34 positive, were consistently CD117 negative. Among the CD34-positive tumors that showed occasional CD117 reactivity were dermatofibrosarcoma protuberans (1 of 7) and hemangiopericytoma (2 of 10). Other mesenchymal tumors that were variably CD117 positive included clear cell sarcoma (7 of 15), metastatic melanoma (9 of 25), and malignant fibrous histiocytoma (1 of 20). These results indicate that CD117 is a specific marker for GIST among tumors that occur in the GI tract and adjacent regions. CD117 expression also separates GISTs from true leiomyomas and gastric schwannomas.