Karjalainen J M, Tammi R H, Tammi M I, Eskelinen M J, Agren U M, Parkkinen J J, Alhava E M, Kosma V M
Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
Am J Pathol. 2000 Sep;157(3):957-65. doi: 10.1016/S0002-9440(10)64608-1.
The cell surface glycoprotein CD44 and its ligand, hyaluronan (HA), enhance growth and metastatic capacity of melanoma cells in vitro, but their clinical significance in primary cutaneous melanoma is still unclear. Therefore, we studied whether the levels of CD44 and HA associate with disease progression and survival of cutaneous melanoma. A series of 292 clinical stage I cutaneous melanomas was analyzed by immunohistochemistry using an anti-CD44H antibody (clone 2C5). HA was demonstrated histochemically using a biotinylated HA-specific affinity probe (bHABC). The reduced staining levels of CD44 and HA were associated with each other and indicators of progressive disease. Reduced CD44 and HA level, high tumor thickness, high pT category, high Clark's level, bleeding, and male gender predicted short univariate recurrence free survival (RFS) and overall survival (OS). In Cox's multivariate analysis (N: = 251), the decreased level of CD44, high tumor thickness, and bleeding predicted independently short RFS. High tumor thickness and bleeding were associated with short OS. We conclude that the reduced cell surface CD44 and HA levels associate with poor prognosis in clinical stage I cutaneous melanoma. The notion that the decreased level of CD44 independently predicts short RFS suggests that reduced cell surface CD44 enhances the spreading potential in localized cutaneous melanoma and that quantification of CD44 offers a prognostic tool for its clinical evaluation.
细胞表面糖蛋白CD44及其配体透明质酸（HA）在体外可增强黑色素瘤细胞的生长和转移能力，但其在原发性皮肤黑色素瘤中的临床意义仍不明确。因此，我们研究了CD44和HA水平是否与皮肤黑色素瘤的疾病进展和生存相关。使用抗CD44H抗体（克隆2C5）通过免疫组织化学分析了一系列292例临床I期皮肤黑色素瘤。使用生物素化的HA特异性亲和探针（bHABC）进行组织化学检测HA。CD44和HA的染色水平降低相互关联且与疾病进展指标相关。CD44和HA水平降低、肿瘤厚度高、pT分类高、Clark分级高、出血以及男性性别预测单因素无复发生存期（RFS）和总生存期（OS）短。在Cox多因素分析（N = 251）中，CD44水平降低、肿瘤厚度高和出血独立预测RFS短。肿瘤厚度高和出血与OS短相关。我们得出结论，细胞表面CD44和HA水平降低与临床I期皮肤黑色素瘤的不良预后相关。CD44水平降低独立预测RFS短这一观点表明，细胞表面CD44水平降低增强了局限性皮肤黑色素瘤的扩散潜能，并且CD44定量为其临床评估提供了一种预后工具。
