Assessment of V600E mutation of BRAF gene and rate of cell proliferation using fine-needle aspirates from metastatic melanomas.

BACKGROUND metastatic melanomas are incurable by systemic treatment and it is therefore of the highest concern to develop new therapeutic regimens. RAF kinases play a key role in the RAS-RAF-MAPK signalling pathway which mediates cellular response to growth signals. An inhibitor of the RAS-RAF-MAPK cascade, sorafenib, has shown promising therapeutic results in treatment of several types of metastatic tumours. It can be hypothesized that metastatic melanomas with activating BRAF mutation may respond to RAF kinase-blocking therapy. The objective of the study was to analyze if the activating BRAF V600E mutation is present in metastatic melanomas. MATERIALS AND METHODS Fine-needle aspirates from 44 metastatic melanomas were studied. The V600E mutation in exon 15 of the BRAF gene was selected for genotyping. A Taq-Man MGB biallelic discrimination system was used. Immunocytochemical assessment of the Ki-67 antigen was used to analyze the growth fraction of cells. RESULTS Nearly 39% of metastatic melanomas had BRAF V600E mutation. Tumours with BRAF V600E mutation had a tendency to have a more aggressive clinical course. The growth fraction showed correlation with tumour progression. This study indicates that the V600E mutation is present in metastatic melanomas and occurs more often in sites without chronic sun exposure. Mutated tumours may have a more aggressive clinical course since such melanomas metastasize at an earlier stage. Determination of the BRAF mutation and the growth fraction of melanomas may add a prognostic value. CONCLUSION A fraction of melanoma cases possess an activating BRAF mutation and may benefit from RAF-kinase inhibitor treatment. Future studies are needed to confirm this hypothesis.