Background: Although several studies have reported the incidence of KIT and PDGFRA gene mutations in cutaneous melanomas of Caucasians, only one report is available for Mongoloids, including Japanese. In Japan, melanoma is an uncommon neoplasm compared with countries with Caucasian populations.
Methods: In this study, protein expression and gene mutations of these two genes were investigated by immunohistochemistry and PCR-direct sequencing in 12 primary cutaneous invasive melanomas of Japanese patients. Acral melanoma was detected in 2 cases, chronically sun-damaged skin melanoma in 3 cases, and non-chronically sun-damaged skin melanoma in 7 cases. Genetic analysis was performed in exons 9, 11, 13, and 17 of the KIT gene and in exons 12 and 18 of the PDGFRA gene.
Results: Point mutations of the KIT gene were recognized in only one (8%) case, codon 559 of exon 11 (GTT → GCT). This is a melanoma of the sole (acral melanoma). No mutations of the PDGFRA gene were recognized. At the protein level, 11 case (92%) showed membranous expression of KIT; the expression did not correlate with melanoma depth. KIT expression was stronger in the peripheral in situ or minimal invasive areas than the central invasive areas. Membranous PDGFRA expression was found in all cases (100%).
Conclusion: In this study, only 8% of melanomas had the KIT mutation in this Japanese population. The finding of a mutation in one of two acral melanomas suggests that KIT inhibitors, for example imatinib, which are already used in clinics for treatment of GIST, can also be used for melanoma.