Fröhlich E, Mack A F, Garbe C, Klessen C
Anatomisches Institut, Osterbergstrasse 3, 72074 Tübingen, Germany.
Br J Dermatol. 2005 Dec;153(6):1159-65. doi: 10.1111/j.1365-2133.2005.06883.x.
Melanomas are heterogeneous tumours, and differentiation from other melanocytic lesions may cause problems. It may be possible that the distribution and/or colocalization pattern of different markers in the lesions can enable a more accurate diagnosis of melanocytic tumours.
To test this hypothesis, melanocytic naevi, primary melanomas and metastases were investigated.
The distribution and colocalization of markers for proliferation, invasion, angiogenesis and motility of the tumour cells were investigated using antibodies directed against actin, cathepsin B (CatB), transforming growth factor-beta, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen/Ki-67 and basic fibroblast growth factor (FGF-2). In addition, melanoma markers (HMB-45 and Melan-A) and proteins unrelated to melanoma progression [epidermal growth factor (EGF) and cathepsin H] were investigated.
Malignant melanomas tended to express more markers of malignancy compared with melanocytic naevi, and the differences were statistically significant for EGF and actin immunoreactivity: melanocytic naevi displayed clear EGF labelling more often (60% vs. 5%) and melanomas showed more intense actin labelling (70% vs. 0%). HMB-45+ cells to a large extent also stained with antibodies to CatB but not to EGF or actin; EGF-, FGF-2- and VEGF-immunoreactive cells were predominantly HMB-45-. Similar combinations were observed in melanocytic naevi and in melanomas.
Labelling with EGF may improve the differential diagnosis of melanocytic neoplasias. However, we did not detect a clear-cut increase of markers of malignancy in melanoma. Cells expressing multiple malignancy markers were also found in some melanocytic naevi; this may confirm the dormant potential of melanocytic naevi for melanoma development.
黑色素瘤是异质性肿瘤,与其他黑素细胞性病变的鉴别可能存在困难。病变中不同标志物的分布和/或共定位模式有可能实现对黑素细胞性肿瘤更准确的诊断。
为验证这一假设,对黑素细胞痣、原发性黑色素瘤和转移瘤进行了研究。
使用针对肌动蛋白、组织蛋白酶B(CatB)、转化生长因子-β、血管内皮生长因子(VEGF)、增殖细胞核抗原/Ki-67和碱性成纤维细胞生长因子(FGF-2)的抗体,研究肿瘤细胞增殖、侵袭、血管生成和运动性标志物的分布及共定位情况。此外,还研究了黑色素瘤标志物(HMB-45和Melan-A)以及与黑色素瘤进展无关的蛋白质[表皮生长因子(EGF)和组织蛋白酶H]。
与黑素细胞痣相比,恶性黑色素瘤倾向于表达更多的恶性标志物,EGF和肌动蛋白免疫反应性的差异具有统计学意义:黑素细胞痣更常出现清晰的EGF标记(60%对5%),而黑色素瘤显示更强的肌动蛋白标记(70%对0%)。HMB-45+细胞在很大程度上也被CatB抗体染色,但不被EGF或肌动蛋白抗体染色;EGF-、FGF-2-和VEGF-免疫反应性细胞主要为HMB-45-。在黑素细胞痣和黑色素瘤中观察到类似的组合。
EGF标记可能有助于改善黑素细胞性肿瘤的鉴别诊断。然而,我们未检测到黑色素瘤中恶性标志物的明显增加。在一些黑素细胞痣中也发现了表达多种恶性标志物的细胞;这可能证实了黑素细胞痣具有发展为黑色素瘤的潜在可能性。