Should BRAFV600E Be Tested in Primary or Metastatic Malignant Melanoma?
Angel Santos-Briz, Elena Godoy, Laura Arango, Patricia Antunez, Eduardo Alcaraz, Emilia Fernandez, M Dolores Ludena. Hospital Universitario de Salamanca, Salamanca, Spain; Hospital Universitario Morales Meseguer, Murcia, Spain
Background: The discovery of BRAFV600 mutation as an oncogenic mutation in cutaneous malignant melanoma (MM) has changed the treatment paradigm for melanoma. Selective BRAF inhibitors have demonstrated response rates far higher than standard chemotherapeutic options. BRAF mutation analysis is usually performed on primary tumour tissue; however, no conclusive data are available on the concordance of test results between primary tumors and corresponding metastases.
Design: Patients with melanoma who underwent surgical resection of the primary tumour and sentinel lymph node biopsy or positive lymphadenectomy were retrospectively recruited from our institution. Formalin-fixed, paraffin-embedded paired samples of primary melanomas and their corresponding lymph node metastases were collected from pathologic archives. For each melanoma, hematoxylin and eosin-stained slides were reviewed. For molecular study, macrodissection of the tumors was performed in all cases. Genomic DNA extraction was conducted from one slide of the tumor block (5m thickness) using cobas® DNA sample Preparation Kit. Mutation status was determined by means of a realtime PCR assay (Cobas 4800 BRAF V600 Mutation Test, Roche Molecular Systems).
Results: 222 tumor tissues from 152 patients with melanoma were screened (median Breslow index=2.5mm). Paired samples of primary melanomas and metastases from the same patients (n =60) were included. BRAF mutations were detected in 91 of 152 primary tumors (59.9%). Among the 60 patients who had paired samples of primary and secondary melanomas, 46 (76,6%) showed consistent mutation patterns between primary tumors and metastatic lesions. Among 22 wild-type tumors, only one case (0.45%) developed BRAFV600E metastases. 13 of 38 (34,2%) BRAFV600E melanomas developed BRAFwild-type metastases.
Conclusions: Our findings show that there is a high concordance in BRAF status between primary BRAFwild-type tumors and their paired metastases; however discordance between primary BRAFV600E tumors and metastatic specimens is not a rare finding. It has been suggested that treatment of tumors not harboring a BRAF mutation could result in the hyperactivation of the MAPK pathway and a possible rapid progression. Therefore, although more extensive studies are necessary, the cases presented might suggest that BRAF testing should be performed in metastatic specimens, even in patients with BRAFV600E primary melanomas.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 36, Tuesday Morning