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[The diagnostic and predictive role of kit (CD117)]
St Dirnhofer1, A Zimpfer, Ph Went
1Institut für Pathologie, Universitätsspital Basel, Basel. sdirnhofer@uhbs.ch
Therapeutische Umschau. Revue Therapeutique
|May 13, 2006
Summary
CD117 (KIT) protein expression is highly specific for gastrointestinal stromal tumors (GIST), with mutations guiding imatinib therapy. Detecting KIT mutations alongside CD117 expression is crucial for accurate diagnosis and targeted treatment.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biology
Background:
- KIT (CD117) is a receptor tyrosine kinase crucial for cell development.
- KIT signaling is vital for hematopoietic progenitor cells, mast cells, and other cell types.
- KIT expression is typically lost upon differentiation, except in specific cell lineages.
Purpose of the Study:
- To highlight the diagnostic and predictive significance of CD117 expression and KIT mutations in GIST.
- To differentiate GIST from other CD117-expressing neoplasms.
- To emphasize the role of molecular diagnostics in guiding targeted therapy.
Main Methods:
- Immunohistochemical detection of CD117 protein expression.
- Analysis of KIT gene mutations, particularly in Exons 11 and 9.
- Correlation of CD117 status with mutational status and therapeutic response.
Main Results:
- Approximately 95% of GISTs are CD117 positive, with high specificity.
- Activating KIT mutations are present in 80-85% of GISTs, primarily in Exons 11 and 9.
- CD117 expression alone is insufficient for targeted therapy; mutational status is key.
Conclusions:
- CD117 expression is a highly sensitive and specific marker for GIST diagnosis.
- KIT mutational analysis is essential for predicting imatinib response in GIST.
- Integrated molecular pathological diagnostics are vital for effective targeted cancer therapy.