CAJ | 학술논문

目的探讨缺氧诱导因子(HIF)1α在肢端恶性黑素瘤(MM)中的表达及其与干细胞因子(SCF)/c-kit途径的关系.方法应用免疫组化法检测HIF-1α在93例MM、21例非肢端MM、39例肢端色素痣组织中的表达,并用15例肢端正常皮肤组织作对照.同时检测c-kit在93例肢端MM组织中的表达情况,采用Spearman相关分析,分析其与HIF-1α的相关性.结果在93例肢端MM中,81例(87.10％)阳性表达HIF-1α,在21例非肢端MM中19例(90.48％)阳性,39例肢端色素痣中6例(15.38％)阳性;15例肢端正常皮肤均为阴性.与肢端正常皮肤和肢端色素痣相比较,肢端MM中HIF-1α的表达增高,差异有统计学意义(均P＜0.01);在肢端MM和非肢端MM组间,HIF-1α表达差异有统计学意义(P＜0.01).HIF-1α表达水平与黑素瘤Clark分级、Breslow厚度分级均呈正相关(rs=0.442,P＜0.01;rs=0.368,P＜ 0.01).在原位、侵袭性、转移性肢端MM组织中,HIF-1α表达水平与肿瘤进展呈正相关(rs=0.420,P＜0.01).在肢端MM中,HIF-1α表达与c-kit表达呈正相关(rs=0.307,P＜ 0.01).结论 HIF-1α蛋白在肢端MM中呈高表达,且与肿瘤的分期、进展、侵袭性均呈正相关,与c-kit在肢端MM组织中的协同表达,提示可能共同参与肢端MM的发病机制.
목적 탐토결양유도인자(HIF)1α재지단악성흑소류(MM)중적표체급기여간세포인자(SCF)/c-kit도경적관계.방법 응용면역조화법검측HIF-1α재93례MM、21례비지단MM、39례지단색소지조직중적표체,병용15례지단정상피부조직작대조.동시검측c-kit재93례지단MM조직중적표체정황,채용Spearman상관분석,분석기여HIF-1α적상관성.결과 재93례지단MM중,81례(87.10％)양성표체HIF-1α,재21례비지단MM중19례(90.48％)양성,39례지단색소지중6례(15.38％)양성;15례지단정상피부균위음성.여지단정상피부화지단색소지상비교,지단MM중HIF-1α적표체증고,차이유통계학의의(균P＜0.01);재지단MM화비지단MM조간,HIF-1α표체차이유통계학의의(P＜0.01).HIF-1α표체수평여흑소류Clark분급、Breslow후도분급균정정상관(rs=0.442,P＜0.01;rs=0.368,P＜ 0.01).재원위、침습성、전이성지단MM조직중,HIF-1α표체수평여종류진전정정상관(rs=0.420,P＜0.01).재지단MM중,HIF-1α표체여c-kit표체정정상관(rs=0.307,P＜ 0.01).결론 HIF-1α단백재지단MM중정고표체,차여종류적분기、진전、침습성균정정상관,여c-kit재지단MM조직중적협동표체,제시가능공동삼여지단MM적발병궤제.
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.