Clinico-Pathological Correlations of BRAF and C-KIT Mutations in Metastatic Melanoma (MM)
Maria D Lozano, Tania Labiano, Myriam Montanana, Nerea Gomez, Mercedes Aguirre, Mariam Maset, Jose I Echeveste, Miguel F Sanmamed, Alfonso Gurpide, Miguel A Idoate, Salvador Martin-Algarra. University of Navarra, Pamplona, Spain
Background: Current advances in the understanding of melanoma gave a solid rationale to introduce different targeted therapies into clinical trials. Patients harbouring BRAF mutations show high response rates after treatment with BRAF inhibitors like Vemurafenid or Dabrafenib. Moreover, clinical experience in patients with mucosal or acral melanomas with gene amplification or activating mutations of c-KIT treated with imatinib, have shown high response rates and prolonged PFS. These results emphasise the importance of molecular information, even in those cases in which the diagnosis was made on small samples obtained through minimally invasive approaches. Cytology is an accurate and cost-effective tool for the diagnosis of metastatic cancer and in many times cytological smears are the only samples available from these patients.
Design: We have studied BRAF in 147 samples of MM from 123 patients by direct sequencing and cobas®4800 BRAF V600 mutation test. Clinicopathological and demographic variables were obtained from our hospital database. DNA extraction was performed from FFPE tissue sections in 85 cases and directly from cytological smears in 62. Comparison between BRAF result in matched paraffin- cytological tumors was performed in 9 cases. CKIT mutations were analyzed in 25 patiens by direct sequencing.
Results: Sixty-three (51.2 %) patients showed BRAF mutations: 48 V600E (76.2 %), 3 V600K (4.76 %), 2 V600R (3.17%) by direct sequencing, and 10 (15.87%) V600 (by Cobas). Eleven patients were treated with BRAF inhibitors within clinical assay. Two cases had CKIT mutations, both mucosal melanomas. BRAF and c-KIT mutations are mutally exclusive. BRAF status did not correlated with primary melanoma histology, gender, age at diagnosis, disease free survival, brain metastases rate and overall survival. Concordance in matched FFPE and cytology was 100%.
Conclusions: The frequency of activating mutations in BRAF is 51.2% in this series. V600E is more frequent, but V600K appears in 4.76 % of the cases. In our series BRAF mutations do not correlate with any clinico-pathological variable sutudied. Mutational analysis of BRAF and c-KIT using cytological samples from patients with metastatic melanoma is feasible regardless of the method of PCR used. It can be used to extend the benefits of targeted therapy to those patients from whom biopsies are not available.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 37, Tuesday Morning