Debate on how to manage pediatric cutaneous melanoma patients continues; particularly in those with sentinel lymph node(SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between pediatric and adult patients suggests that melanoma in pediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences.
We investigated the epigenetic(methylation) regulation of several tumor-related genes(TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases(n=17) and primary tumors(n=20) of pediatric melanoma patients to determine their clinical relevance.
AJCC Stage I-III(n=37) pediatric cutaneous melanoma patients(≤ 21 years at diagnosis) were analyzed. Gene promoter methylation of TRGs: RASSF1A, RARβ2, WIF1, and APC was evaluated.
Hypermethylation of RASSF1A, RARβ2, WIF1, and APC in histopathology(+) SLNs was 29.4%(5/17), 25%(4/16), 25%(4/16), and 18.8%(3/16), respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) pediatric melanoma patients was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) pediatric melanoma patients with hypermethylation of >1 TRGs versus ≤1 TRG had worse disease-free(p=0.02) and overall survival(p=0.02).
Differences in the methylation status of these TRGs in the SLN(+) pediatric and adult melanoma patients may account for why SLN(+) pediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) pediatric melanoma patients, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.