Tumor antigen expression in melanoma varies according to antigen and stage
Tumor antigen expression in melanoma varies according to antigen and stage
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DOI：
10.1158/1078-0432.ccr-05-1544
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发表时间：
2006-02-01
影响因子：
11.5
通讯作者：
Cebon, J
中科院分区：
文献类型：
--
作者：
Barrow, C;Browning, J;Cebon, J
目的：黑色素瘤细胞表达可诱导T细胞和抗体应答的抗原。如果这些分子是有用的免疫治疗的melanoma.Experimental Design：恶性黑色素瘤（n = 586）从426例患者的抗原表达进行了分型。可从86个个体获得多个样品，从而能够分析随时间推移的抗原表达模式。石蜡包埋标本行免疫组化检测分化抗原gp 100、Melan-A、酪氨酸酶和“癌/睾丸”抗原MAGE-A1、MAGE-A4和NY-ESO-1的存在。转移瘤（n = 71）和远处转移瘤（n = 90）。分化抗原在93%至95%的肿瘤中强烈表达，与阶段无关。相反，MAGE-A1、MAGE-A4和NY-ESO-1在原发性肿瘤中的癌/睾丸抗原表达频率较低（分别为20%、9%和45%）。MAGE-A1和MAGE-A4在疾病进展时获得（在远处转移中分别为51%和44%），但NY-ESO-1没有获得，NY-ESO-1在45%中保持阳性。MAGE-A1的表达是两倍的流行性溃疡的原发性非溃疡的原发性（30%对15%; P = 0.006）和厚，而不是薄黑色素瘤（26%对10%; P = 0.1）。这将有助于为黑色素瘤免疫治疗临床试验的患者和靶抗原选择提供信息。
Purpose: Melanoma cells express antigens that can induce T-cell and antibody responses. Obtaining a detailed understanding of antigen expression in primary and metastatic melanoma is essential if these molecules are to be useful targets for immunotherapy of melanoma.Experimental Design: Malignant melanomas (n = 586) from 426 patients were typed for antigen expression. Multiple samples were available from 86 individuals, enabling analysis of antigen expression patterns over time. Paraffin-embedded samples were tested by immunohistochemistry for the presence of the differentiation antigens: gp100, Melan-A, tyrosinase, and the "cancer/testis" antigens MAGE-A1, MAGE-A4, and NY-ESO-1.Results: Samples were primary tumors (n = 251), lymph node metastases (n = 174), s.c. metastases (n = 71), and distant metastases (n = 90). The differentiation antigens were strongly expressed in 93% to 95% of tumors regardless of stage, In contrast, the frequency of cancer/ testis antigen expression in primary tumors for MAGE-A1, MAGE-A4, and NY-ESO-1 was lower (20%, 9%, and 45%, respectively). MAGE-A1 and MAGE-A4 were acquired with advancing disease (to 51% and 44% in distant metastases, respectively) but not NY-ESO-1, which remained positive in 45%. MAGE-A1 expression was twice as prevalent in ulcerated primaries as in nonulcerated primaries (30% versus 15%; P = 0.006) and in thicker as opposed to thin melanomas (26% versus 10%; P = 0.1).Conclusions: This large series describes patterns of antigen expression in melanoma and their evolution over time. This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials.