1123P - BRAF-V600 and c-KIT mutation analysis in cytologycal samples from metastatic melanoma

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Biomarkers
Melanoma and other Skin Tumours
Pathology/Molecular Biology
Presenter Tania Labiano
Authors T. Labiano1, M.D. Lozano1, J.I. Echeveste1, M. Montañana1, M.F. Sanmamed2, E. Castanon Alvarez3, N. Gómez1, A. Gurpide2, M.A. Idoate1, S. Martin Algarra4
  • 1Pathology, University of Navarra, 31080 - Pamplona/ES
  • 2Medical Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 3Oncology Department, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 4Clinica Universidad de Navarra, 31008 - Pamplona/ES

Abstract

Background

Vemurafenib is approved for the first-line treatment of BRAF-V600E+ metastatic melanoma (MM). Also, preliminary clinical experience with imatinib in MM patients with gene amplification or activating mutations of c-KIT, have shown high response rates and prolonged progression free survival. These results emphasise the importance of molecular information, even in those cases in which the diagnosis is made on small samples obtained through minimally invasive approaches. Cytology is an accurate and cost-effective tool for the diagnosis of MM and cytological smears are occasionally the only samples available from these patients.

Methods

We have studied BRAF and c-KIT mutations in 62 cytological samples from MM patients. Preliminary results of 56 cases (32 men (58%) and 23 women (42%); median age 52 years) are included in this abstract. Diagnosis was made on fine needle aspiration in 41 cases, imprints in 10, direct eye touch in 1, a smear from cellular culture in 1, and pleural and peritoneal fluid in 3. To assure tissue quality, DNA was extracted directly from Papanicolau stained smears on which cytological diagnosis was made. BRAF and c-KIT mutations were analysed by PCR and direct sequencing using an ABI PRISM TM 310XL.

Results

BRAF mutations was found in 30 cases (53.5%): V600E mutation in 26 (86,7%) and V600K in 4 (13,3%). c-KIT mutations were studied in 18 cases. L576P mutation was present in 1 patient with liver metastasis from acral melanoma (5.56%). BRAF status did not correlated with primary melanoma histology, age at diagnosis, disease free survival, brain metastases rate and overall survival.

Conclusions

The frequency of activating mutations in BRAF is 53.5% in this series. V600E is the most commonly observed mutations, but V600K appears in 13.3% of the cases. c-KIT mutations incidence is low (5.56%). Mutational analysis of BRAF and c-KIT using cytological samples from patients with metastatic melanoma is feasible and can be used to extend the benefits of targeted therapy to those patients from which biopsies are not available. Updated results will be presented.

Disclosure

S. Martin Algarra: Participation in Advisory Boards of Roche.

All other authors have declared no conflicts of interest.