Sviatoha V, Rundgren A, Tani E, Hansson J, Kleina R, Skoog L
Department of General Pathology, Latvian Centre of Pathology, Latvian Medical Academy, Riga.
Cytopathology. 2002 Feb;13(1):11-21. doi: 10.1046/j.1365-2303.2002.00376.x.
The clinical behaviour of melanoma is often unpredictable using clinical and histological criteria. Tumour cell markers related to cell cycle regulation, apoptosis, cell-cell interactions and cell proliferation might improve the possibility of predicting the clinical course of melanoma. The aim of the present study was to refine prognostic criteria by an immunocytochemical investigation of CD44, CD40, bcl-2 antigens and cell proliferation in tumour cells aspirated from metastases of malignant melanoma. CD40 is a cell surface receptor shown to be expressed by lymphomas as well as carcinomas, and is thought to play a central role in the process of tumour progression. CD44 is a transmembrane glycoprotein, which is involved in growth signal transmission of importance in the binding of tumour cells to endothelium, cell migration and enhancement of cell motility, which makes it of interest to study in relation to the metastasizing capacity of tumours. The bcl-2 protein is active in the process of programmed cell death (apoptosis) as an antiapoptotic agent and its expression may reflect tumour progression. Mean/median percentages of tumour cell positivity were 8.5/3.0 for CD40, 76.1/86.3 for CD44 and 7.4/3.3 for bcl-2. A significant correlation was observed between expression of apoptosis-associated bcl-2 antigen and overall survival (r = 0.33). The CD44 positive cell fraction was higher in patients with short overall survival than those with long survival but this difference was not statistically significant. The expression of CD40 did not correlate with overall survival. The mean/median proliferation fraction assessed by MIB-1 monoclonal antibody was 25.8/23.9 and showed a significant correlation with survival after diagnosis of melanoma metastasis (r = 0.32). Lack of bcl-2 expression and a high proportion of tumour cells expressing Ki-67 antigen are predictors of poor prognosis that are independent of the traditionally accepted Breslow's thickness of the primary melanomas.
使用临床和组织学标准往往难以预测黑色素瘤的临床行为。与细胞周期调控、细胞凋亡、细胞间相互作用及细胞增殖相关的肿瘤细胞标志物，可能会提高预测黑色素瘤临床病程的可能性。本研究的目的是通过对恶性黑色素瘤转移灶穿刺所得肿瘤细胞中的CD44、CD40、bcl-2抗原及细胞增殖进行免疫细胞化学研究，以完善预后标准。CD40是一种细胞表面受体，已证实其在淋巴瘤和癌中均有表达，且被认为在肿瘤进展过程中起核心作用。CD44是一种跨膜糖蛋白，参与生长信号传递，在肿瘤细胞与内皮细胞的结合、细胞迁移及细胞运动增强中具有重要作用，这使得研究其与肿瘤转移能力的关系具有重要意义。bcl-2蛋白作为一种抗凋亡因子，在程序性细胞死亡（凋亡）过程中发挥作用，其表达可能反映肿瘤进展情况。肿瘤细胞CD40阳性的平均/中位数百分比为8.5/3.0，CD44为76.1/86.3，bcl-2为7.4/3.3。观察到凋亡相关bcl-2抗原的表达与总生存期之间存在显著相关性（r = 0.33）。总生存期短的患者中CD44阳性细胞比例高于生存期长的患者，但这种差异无统计学意义。CD40的表达与总生存期无关。通过MIB-1单克隆抗体评估的平均/中位数增殖分数为25.8/23.9，且与黑色素瘤转移诊断后的生存期存在显著相关性（r = 0.32）。bcl-2表达缺失及高比例表达Ki-67抗原的肿瘤细胞是预后不良的预测指标，且独立于传统认可的原发性黑色素瘤的Breslow厚度。
