van den Oord J J, Maes A, Stas M, Nuyts J, De Wever I, De Wolf-Peeters C
Department of Pathology II, University Hospital St Rafael, KUL, Leuven, Belgium.
Melanoma Res. 1997 Apr;7(2):121-8. doi: 10.1097/00008390-199704000-00006.
The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not all cancers in man. To investigate the role of NM23 in the progression of human malignant melanoma, we studied the expression and distribution of the nm23 protein with a sensitive immunohistochemical technique and a well-characterized monoclonal antibody in 41 benign pigment cell lesions and 71 uniformly treated malignant melanomas with a long follow up-up. In benign naevi, the junctional nests frequently expressed nm23 protein, whereas the immunoreactivity tended to decrease when the lesions matured. All malignant melanomas expressed nm23 protein in their vertical and/or radial growth phases, and the immunoreactivity tended to increase towards the deeper parts of the lesion. No relation was found between nm23 expression and patient outcome. In addition, nm23 was found in activated lymphoid cells, and this feature was significantly associated with a brisk lymphocytic stroma response in malignant melanomas. Our data are at variance with previous mRNA studies on malignant melanoma, and indicate that routine immunohistochemical analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be used as a prognostic marker for patients suffering from malignant melanoma. In contrast, our findings suggest that the nm23 protein in pigment cell lesions is related to the proliferative or activated state of pigment cells, rather than to their metastatic potential.
编码红细胞核苷二磷酸激酶A和B的NM23基因,在肿瘤进展的实验动物模型以及部分(而非全部)人类癌症中,已被发现具有转移抑制基因的作用。为了研究NM23在人类恶性黑色素瘤进展中的作用,我们采用一种灵敏的免疫组织化学技术以及一种特性明确的单克隆抗体,对41例良性色素细胞病变和71例经过统一治疗且随访时间较长的恶性黑色素瘤进行研究,观察nm23蛋白的表达和分布情况。在良性痣中,交界巢常常表达nm23蛋白,而随着病变成熟,免疫反应性往往会降低。所有恶性黑色素瘤在其垂直和/或放射状生长阶段均表达nm23蛋白,且免疫反应性往往朝着病变的深部增加。未发现nm23表达与患者预后之间存在关联。此外,在活化的淋巴细胞中发现了nm23,这一特征与恶性黑色素瘤中活跃的淋巴细胞间质反应显著相关。我们的数据与先前关于恶性黑色素瘤的mRNA研究结果不同,表明对石蜡包埋肿瘤组织进行nm23蛋白的常规免疫组织化学分析不能可靠地用作恶性黑色素瘤患者的预后标志物。相反,我们的研究结果表明,色素细胞病变中的nm23蛋白与色素细胞的增殖或活化状态有关,而非与其转移潜能有关。