中华皮肤科杂志 ›› 2014, Vol. 47 ›› Issue (9): 615-618.

• 论著 • 上一篇    下一篇

缺氧诱导因子1α在肢端恶性黑素瘤组织中的表达

周璐1,胡彬2,黄莹雪3,邵雪宝4,李阿梅5,陈浩4,孙建方4   

  1. 1. 青岛大学附属医院皮肤科
    2. 中国医学科学院北京协和医学院皮肤病研究所
    3. 中南大学湘雅医院皮肤科
    4. 南京 中国医学科学院北京协和医学院皮肤病研究所
    5. 南京市 中国医学科学院皮肤病研究所
  • 收稿日期:2014-01-17 修回日期:2014-05-12 出版日期:2014-09-15 发布日期:2014-09-01
  • 通讯作者: 陈浩 E-mail:ch76ch@163.com
  • 基金资助:
    国家自然科学基金

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

  • Received:2014-01-17 Revised:2014-05-12 Online:2014-09-15 Published:2014-09-01

摘要: 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。

关键词: 黑色素瘤, 缺氧诱导因子1,α亚基, 原癌基因蛋白质c-kit

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