Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
Melanoma Res. 2011 Dec;21(6):491-501. doi: 10.1097/CMR.0b013e32834bf37b.
The characterization of factors involved in the etiology of melanoma may lead to the identification of new targets for therapy and prognostic markers. Recent data indicate that Nodal can be expressed by malignant melanoma cells and this expression seems to contribute to melanoma development and progression. The aim of this study was to investigate the potential of Nodal as a prognostic marker for stage III/IV patients and as a treatment target for melanoma immunotherapy. We analyzed, by means of immunohistochemistry, 63 patients with stage III/IV melanoma for expression of Nodal in their tumors taken during the course of their disease. Furthermore, to research potential safety issues when immunotherapeutically targeting Nodal, we assessed Nodal expression in normal human adult tissues. We found that Nodal can be expressed at all stages of melanoma progression and there is no significant increase in the frequency of Nodal expression in distant metastases. Furthermore, our data show that there is no correlation between the expression of Nodal during course of disease and survival of patients. Finally, when screening for Nodal expression in normal adult organ tissues, we found consistent expression in renal tissue. We conclude that Nodal expression cannot be used as a prognostic marker for survival of patients with stage III/IV melanoma and as this putative target is renally expressed, it is not well-suited for immunotherapeutic approaches. This study suggests that, despite strong previous suggestions, the role of Nodal in melanoma progression may be less prominent and immunotherapeutic targeting of Nodal could be potentially harmful.
黑色素瘤病因相关因素的特征分析可能有助于确定新的治疗靶点和预后标志物。最近的数据表明，Nodal 可在恶性黑色素瘤细胞中表达，这种表达似乎有助于黑色素瘤的发展和进展。本研究旨在探讨 Nodal 是否可作为 III/IV 期患者的预后标志物和黑色素瘤免疫治疗的治疗靶点。我们通过免疫组化分析了 63 例 III/IV 期黑色素瘤患者肿瘤组织中 Nodal 的表达情况。此外，为了研究针对 Nodal 的免疫治疗的潜在安全性问题，我们评估了 Nodal 在正常成人组织中的表达。结果发现，Nodal 可在黑色素瘤进展的所有阶段表达，并且在远处转移中 Nodal 的表达频率没有明显增加。此外，我们的数据表明，Nodal 在疾病过程中的表达与患者的生存之间没有相关性。最后，当在正常成人器官组织中筛查 Nodal 的表达时，我们发现肾脏组织中有一致的表达。我们得出结论，Nodal 的表达不能作为 III/IV 期黑色素瘤患者生存的预后标志物，而且由于该假定靶点在肾脏中表达，因此不适合免疫治疗方法。本研究表明，尽管之前有强烈的暗示，但 Nodal 在黑色素瘤进展中的作用可能不那么突出，针对 Nodal 的免疫治疗可能具有潜在的危害。
