Schadendorf D, Heidel J, Gawlik C, Suter L, Czarnetzki B M
Department of Dermatology, University Hospital Rudolf Virchow, Freie Universität Berlin, Federal Republic of Germany.
J Natl Cancer Inst. 1995 Mar 1;87(5):366-71. doi: 10.1093/jnci/87.5.366.
The process of tumor growth and metastasis is a complex multistep cascade. The ability of tumor cells to adhere to and detach from extracellular matrix and endothelial cells may be crucial in the metastatic process and may dramatically alter the clinical prognosis and outcome for patients with certain cancers. A number of adhesion molecules have been detected on human melanoma cells and have been associated with various properties in vitro including invasiveness. Recent findings from our laboratory have indicated an ordered change in integrin expression during the process of tumor progression.
This study was designed to identify molecular markers present on human melanoma cells and in intratumoral vessels that have prognostic significance regarding disease-free interval and survival time.
Specimens of primary cutaneous malignant melanoma were obtained from 60 patients who had been followed for at least 36 months, with development of metastases in 29 patients during that period of time, and were analyzed for their expression of VLA-4, VLA-6, ICAM-1, ELAM-1 (E-selectin), CD62 (P-selectin), and CD44v6 molecules on tumor and endothelial cells by immunostaining. Light microscopy was used to evaluate and categorize the number of positively stained cells. Statistical analyses were done to determine the relationship of the expression of individual adhesion molecules with time to disease progression (i.e., disease-free interval) and overall survival time.
In each case, positive staining for ELAM-1 and CD62 on intratumoral vessels and for VLA-4 on human melanoma cells was negatively associated with disease-free interval (P < .01) and overall survival time (P < .01). The presence of VLA-6, CD44v6, and ICAM-1 on melanoma cells was not associated with clinical outcome.
Immunohistochemical screening and detection of ELAM-1, CD62, and VLA-4 may help to define a subgroup of melanoma patients at risk of developing metastases.
肿瘤生长和转移过程是一个复杂的多步骤级联反应。肿瘤细胞与细胞外基质及内皮细胞黏附与脱离的能力在转移过程中可能至关重要，并且可能显著改变某些癌症患者的临床预后和结局。在人类黑色素瘤细胞上已检测到多种黏附分子，并且它们在体外与包括侵袭性在内的各种特性相关。我们实验室最近的研究结果表明，在肿瘤进展过程中整合素表达存在有序变化。
本研究旨在鉴定人类黑色素瘤细胞和肿瘤内血管上存在的、对无病生存期和生存时间具有预后意义的分子标志物。
从60例随访至少36个月的原发性皮肤恶性黑色素瘤患者获取标本，在此期间29例患者发生转移，通过免疫染色分析肿瘤细胞和内皮细胞上VLA-4、VLA-6、ICAM-1、ELAM-1（E-选择素）、CD62（P-选择素）和CD44v6分子的表达。用光镜评估并分类阳性染色细胞的数量。进行统计分析以确定各个黏附分子的表达与疾病进展时间（即无病生存期）和总生存时间之间的关系。
在每种情况下，肿瘤内血管上ELAM-1和CD62以及人类黑色素瘤细胞上VLA-4的阳性染色与无病生存期（P <.01）和总生存时间（P <.01）呈负相关。黑色素瘤细胞上VLA-6、CD44v6和ICAM-1的存在与临床结局无关。
ELAM-1、CD62和VLA-4的免疫组织化学筛查和检测可能有助于确定有发生转移风险的黑色素瘤患者亚组。
