Clinical and molecular characteristics and metastatic pathways in patients with cutaneous melanoma

Introduction: Cutaneous melanoma can metastasise haematogenously and/or lymphogenously to form satellite/in-transit, lymph node or distant metastasis. The primary aim of this study was to determine if BRAF and NRAS-mutant tumours behave differently to wild-type (WT) tumours in their site of first tumour recurrence.
Methods: Prospective cohort study of patients with a histologically confirmed primary cutaneous melanoma diagnosed within six-months of presentation to one of three tertiary referral centres in Victoria, Australia from 2010-2015. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded.
Results: Of 1,544 patients, 429 (27.8%) developed metastasis over a median 4.6 year follow-up. Of these, 101 (23.5%), 275 (64.1%) and 53 (12.4%) developed detected distant, regional lymph node and satellite/in-transit metastasis as the first site of metastasis, respectively. Among the entire cohort, 40.6% and 18.2% of tumours were BRAF and NRAS mutant, respectively. BRAF mutation was associated with age<50 years (OR 2.46, 95%CI 1.87-3.22, p<0.001) and superficial spreading subtype (OR 2.45, 95%CI 1.29-4.65, p=0.006). Similar proportions of the site of first metastasis were seen among patients with BRAF mutant and BRAF WT tumours (9.0%, 67.1% and 24.0% vs. 15.9%, 59.8% and 24.3%, for satellite/in-transit, regional lymph node and distant metastasis, respectively, p=0.11). Similar findings were seen for NRAS mutation status (15.5%, 65.5% and 19.0% vs. 12.8%, 62.0% and 22.2%, p=0.6).
Conclusion: Tumour mutation status was not related to the site of first tumour recurrence. While tumour mutation status is associated with specific clinicopathological characteristics, information on the somatic mutational profile may not assist with predicting the route of metastasis.

Dr. Nikki Adler