Expression of hypoxia-inducible factor-1α in acral malignant melanoma tissue

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