High frequency of melanoma-associated antigen or HLA class I loss does not correlate with survival in primary melanoma
High frequency of melanoma-associated antigen or HLA class I loss does not correlate with survival in primary melanoma
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DOI：
10.1097/00002371-200401000-00007
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Nestle, FO
中科院分区：
文献类型：
--
作者：
Hofbauer, GFL;Burkhart, A;Nestle, FO
黑色素瘤相关抗原是许多黑色素瘤免疫试验的中心。关于抗原表达对疾病自然病程的影响知之甚少。我们对110例原发性黑色素瘤进行了黑色素瘤相关抗原gp 100、MelanA/MART-1、法师-3、酪氨酸酶和HLA I类分子染色，中位随访时间为13年（范围10-18年）。在91例评估的病例中，我们发现gp 100、MelanA/MART-1和酪氨酸酶的免疫反应性分别在88%、80%和87%的原发性肿瘤中，法师-3的免疫反应性在37%的原发性肿瘤中，HLA I类的免疫反应性在86%的原发性肿瘤中。缺失，即原发性肿瘤内的异质性表达，对于gp 100（原发性肿瘤的73%）最明显，而对于法师-3（原发性肿瘤的27%）最少。MelanA/MART-1和酪氨酸酶表达缺失分别占原发性肿瘤的58%和59%。HLA I类表达缺失率高（74%）。对原发性肿瘤中的表达和黑色素瘤抗原的丢失以及个体原发性肿瘤中的HLA I类的单变量和多变量统计分析显示，与总生存期无显著相关性。gp 100的损失和酪氨酸酶表达的损失表现出负面的生存趋势超过这些抗原的均匀表达，虽然没有达到统计学意义（P = 0.08和P = 0.09，分别）。我们的结论是，黑色素瘤抗原表达以及HLA I类表达的损失是一个经常观察原发性黑色素瘤。然而，在我们的队列中，在个体原发性肿瘤中这些抗原的丢失与对总生存率的负面影响之间没有统计学显著相关性。
Melanoma-associated antigens are at the center of many immunotherapeutic trials in melanoma. Little is known about the impact of antigen expression on the natural course of disease. We stained 110 cases of primary melanoma with a median follow-up of 13 years (range 10-18 years) for melanoma-associated antigens gp100, MelanA/MART-1, MAGE-3, tyrosinase, and for HLA class I molecules. Of 91 cases evaluated, we found immunoreactivity for gp 100, MelanA/MART-1, and tyrosinase in 88%, 80%, and 87% of primary tumors, respectively, for MAGE-3 in 37% and for HLA class I in 86% of primary tumors. Loss, that is, heterogeneous expression within primary tumors, was most pronounced for gp 100 (73% of primary tumors) and least for MAGE-3 (27% of primary tumors). MelanA/MART-1 and tyrosinase expression loss was 58% and 59% of primary tumors, respectively. There was a high rate of expression loss for HLA class I (74%). Univariate and multivariate statistical analysis of expression in primary tumors and loss of melanoma antigens as well as HLA class I in individual primary tumors showed no significant correlation to overall survival. Loss of gp100 and loss of tyrosinase expression showed a negative survival trend over homogeneous expression of these antigens, although not reaching statistical significance (P = 0.08 and P = 0.09, respectively). We conclude that loss of melanoma antigen expression as well as HLA class I expression is a frequent observation in primary melanoma. However, no statistically significant correlation between loss of these antigens in individual primary tumors and negative impact on overall survival was found in our cohort.