Abstract: Zhou Lu, Hu Bin, Huang Yingxue, Shao Xuebao, Li Amei, Chen Hao, Sun Jianfang*. *Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China Corresponding author: Chen Hao, Email: ch76ch@163.com; Sun Jianfang, Email: sunjf57@163.com 【Abstract】 Objective To measure the expression of hypoxia-inducible factor （HIF）-1α in acral malignant melanoma （MM） tissue and to investigate its relationship with the stem cell factor （SCF）/c-kit pathway. Methods Immunohistochemical staining was performed to measure the expression of HIF-1α in tissue specimens from lesions of 93 patients with acral MM, 21 with non-acral MM, 39 with acral melanocytic nevi, and from the normal acral skin of 15 healthy human controls. Meanwhile, the expression of c-kit was detected by immunohistochemical staining in the 93 acral MM tissue specimens. Statistical comparisons were carried out by chi-square test and Mann-Whitney U test. The relationship of HIF-1α expression with c-kit expression as well as tumor progression and staging was assessed by Spearman correlation analysis. Results Immunohistochemistry showed that the expression rate of HIF-1α was 87.10% （81/93） in acral MM specimens, 90.48% （19/21） in non-acral MM specimens, 15.38% （6/39） in acral melanocytic nevus specimens, but 0 （0/15） in the normal acral skin specimens. The expression of HIF-1α was significantly higher in acral MM lesions than in normal acral skin and acral melanocytic nevus lesions （both P < 0.01）, and significantly different between acral MM and non-acral MM lesions （P < 0.01）. Moreover, HIF-1α expression was positively correlated with Clark level and Breslow depth of melanoma （rs = 0.442, 0.368，respectively, both P < 0.01）, with the progression of acral MM （from in situ to aggressive and metastatic MM） （rs = 0.420, P < 0.01）, and with the expression of c-kit （rs = 0.307, P < 0.01）. Conclusions HIF-1α is highly expressed in acral MM, positively correlated with the staging, progression and aggression of MM, and co-expressed with c-kit in acral MM tissue, suggesting that both HIF-1α and c-kit take part in the pathogenesis of acral MM.

Key words: Melanoma, Hypoxia-inducible factor 1, alpha subunit, Proto-oncogene proteins c-kit