Marker specific for Gastrointestinal Stromal Tumor (GIST): September 2012
## **Core Concept**
Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They originate from the interstitial cells of Cajal or their precursors. GISTs are characterized by mutations in specific genes, most commonly the **KIT** gene or the **PDGFRA** gene, which lead to the constitutive activation of tyrosine kinase receptors.
## **Why the Correct Answer is Right**
The correct answer, **CD117 (c-KIT)**, is a marker specific for GIST because it is a transmembrane receptor tyrosine kinase, and mutations in the **KIT** gene are found in about 80-90% of GISTs. These mutations lead to the overexpression of the CD117 protein on the surface of GIST cells, making **CD117 (c-KIT)** a sensitive and specific marker for the diagnosis of GIST.
## **Why Each Wrong Option is Incorrect**
- **Option A: CD34** - While CD34 is a marker that can be positive in GISTs, it is not specific for GIST as it can also be positive in other tumors and normal hematopoietic progenitor cells.
- **Option B: S-100** - S-100 is a marker more commonly associated with neural crest-derived tumors, such as melanomas and schwannomas, and is not specific for GIST.
- **Option D: SMA (Smooth Muscle Actin)** - SMA is a marker for smooth muscle differentiation and can be positive in leiomyomas and leiomyosarcomas, which are different from GISTs.
## **Clinical Pearl / High-Yield Fact**
A key clinical pearl is that GISTs are often resistant to traditional chemotherapy and radiotherapy but have a good response to targeted therapy with **tyrosine kinase inhibitors (TKIs)**, such as imatinib, which specifically inhibit the KIT and PDGFRA tyrosine kinases.
## **Correct Answer:** . **CD117 (c-KIT)**