Correlation of KIT Expression and KIT Gene Mutations in Acral Lentiginous and Mucosal Melanomas
S Abu-Abed, F Wright, T Petrella, A Seth, W Hanna. Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Background: KIT gene mutations have been reported in 19% of mucosal melanoma (MM) and 15% of acral lentiginous melanoma (ALM) cases. Since patients with gastrointestinal stromal tumours have a significant survival benefit following treatment with the tyrosine kinase inhibitor, Gleevac (imatinib mesylate, STI571), several clinical trials have offered Gleevac to patients with melanoma. Early results show a near complete response to treatment with Gleevac in patients harboring KIT gene mutations in either exons 11 or 13, irrespective of whether KIT expression was detected by immunohistochemistry (IHC). The goal of this project is to correlate KIT expression to KIT gene mutations in ALM and MM cases treated at the Sunnybrook Health Sciences Centre between 1990 to present date.
Design: Paraffin-embedded tissue from ALM and MM cases was retrieved from the archives. Histological assessment included routine H&E stains, as well as IHC staining for KIT. Genomic DNA extracted from tumor-rich areas was used for PCR-based amplification of exons 11 and 13. The PCR-amplified products were sequenced and analyzed for mutations.
Results: We have identified 60 ALM and MM cases, of which 78.33% are positive for KIT expression.
Amplification of exon 11 has been successfully completed in 6 cases, 2 of which show the following mutations: M551K and N566D.
Conclusions: While studies have shown that KIT expression alone does not predict responsiveness to treatment with Gleevac, more recent clinical trials have demonstrated a near complete response to treatment in melanoma cases that harbor KIT gene mutations in exons 11 or 13. We hope that findings from our study will build upon the rationale for routine screening of patients with melanoma for both KIT expression and KIT gene mutations, possibly allowing for targeted treatment with either Gleevac or other tyrosine kinase inhibitors developed in the future.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 59, Monday Morning