Expression and mutation analysis of the c-kit gene in acral cutaneous malignant melanoma

Abstract

Objective To analyze the frequency and type of mutations in the c-kit gene, and to measure the expression of c-kit protein in patients with acral malignant melanoma. Methods Skin tissue specimens were collected from the lesions of 115 patients with cutaneous malignant melanoma（CMM）and 30 patients with acral melanocytic nevi, as well as normal skin of 15 healthy human controls. PCR and DNA sequencing were performed to analyze the sequence of the c-kit gene, and immunohistochemical staining was conducted to observe c-kit protein expression in tissue samples. Statistical analysis was done by Chi-square test, Mann-Whitney U test and Spearman's rank correlation test. Results C-kit protein was expressed in 90.3%（84/93）of acral CMM specimens, 81.8%（18/22）of non-acral CMM specimens, and 63.3%（19/30）of acral melanocytic nevus specimens. Among 58 acral invasive CMM specimens, 29 showed strong expression of c-kit protein in tumor cells at the dermal-epidermal junction, 8 showed negative or weak c-kit expression in invasive and infiltrating tumor cells in the dermis. The expression rate of c-kit protein was significantly higher in acral CMM specimens than in acral melanocytic nevus specimens（χ2 = 12.14, P 0.05）. C-kit gene mutations were detected in 4 out of the 115 CMM cases, including L576P mutation in 3 cases and K642E mutation in 1 case. All the 4 patients carrying mutations were diagnosed as acral CMM, and exhibited diffuse and strong expression of c-kit protein. Conclusions The expression of c-kit protein is stronger in acral than in non-acral invasive CMM lesions. All the mutations detected in these cases are common types of c-kit mutations in acral CMM, but the mutation frequency is lower than that reported in foreign literature. Key words: Melanoma; Nevus, pigmented; Proto-oncogene proteins c-kit; Point mutation; C-kit gene