BACKGROUND: Debate on how to manage paediatric patients with cutaneous melanoma 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 paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. OBJECTIVES: We investigated the epigenetic (methylation) regulation of several tumour-related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. METHODS: Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I-III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARβ2, WIF1 and APC was evaluated. RESULTS: Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease-free (P = 0·02) and overall survival (P = 0·02). CONCLUSIONS: Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.
BACKGROUND: Debate on how to manage paediatric patients with cutaneous melanoma 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 paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. OBJECTIVES: We investigated the epigenetic (methylation) regulation of several tumour-related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. METHODS: Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I-III cutaneous melanoma were analysed. Gene promoter methylation of the TRGsRASSF1A, RARβ2, WIF1 and APC was evaluated. RESULTS: Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease-free (P = 0·02) and overall survival (P = 0·02). CONCLUSIONS: Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.
Authors: Vernon K Sondak; Jeremy M G Taylor; Michael S Sabel; Yue Wang; Lori Lowe; Amelia C Grover; Alfred E Chang; Alan M Yahanda; James Moon; Timothy M Johnson Journal: Ann Surg Oncol Date: 2004-03 Impact factor: 5.344
Authors: F F Haddad; A Stall; J Messina; A Brobeil; E Ramnath; L F Glass; C W Cruse; C G Berman; D S Reintgen Journal: Ann Surg Oncol Date: 1999-03 Impact factor: 5.344
Authors: Stacey Moore-Olufemi; Cynthia Herzog; Carla Warneke; Jerry E Gershenwald; Paul Mansfield; Merrick Ross; Victor Prieto; Kevin P Lally; Andrea Hayes-Jordan Journal: Ann Surg Date: 2011-06 Impact factor: 12.969
Authors: Dave S B Hoon; Mia Spugnardi; Christine Kuo; Sharon K Huang; Donald L Morton; Bret Taback Journal: Oncogene Date: 2004-05-13 Impact factor: 9.867
Authors: Jasper Wouters; Miguel Vizoso; Anna Martinez-Cardus; F Javier Carmona; Olivier Govaere; Teresa Laguna; Jesuchristopher Joseph; Peter Dynoodt; Claudia Aura; Mona Foth; Roy Cloots; Karin van den Hurk; Balazs Balint; Ian G Murphy; Enda W McDermott; Kieran Sheahan; Karin Jirström; Bjorn Nodin; Girish Mallya-Udupi; Joost J van den Oord; William M Gallagher; Manel Esteller Journal: BMC Med Date: 2017-06-05 Impact factor: 8.775