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使用抗皮肤黑色素瘤相关抗原和抗 HLA 单克隆抗体分析葡萄膜黑色素瘤病变的抗原谱。

Analysis of the antigenic profile of uveal melanoma lesions with anti-cutaneous melanoma-associated antigen and anti-HLA monoclonal antibodies.

作者信息

Natali P G, Bigotti A, Nicotra M R, Nardi R M, Delovu A, Segatto O, Ferrone S

机构信息

Department of Immunology, Regina Elena Cancer Institute, Rome, Italy.

出版信息

Cancer Res. 1989 Mar 1;49(5):1269-74.

PMID:2917356
Abstract

The reactivity of 12 surgically removed uveal melanoma lesions with monoclonal antibodies (MoAb) to 14 membrane-bound and 2 cytoplasmic cutaneous melanoma-associated antigens (MAA), to the 2 subunits of HLA Class I antigens and to the gene products of the HLA-D region was compared with that of cutaneous melanoma lesions and correlated with their histiotype. The membrane-bound determinants defined by the anti-Mr 92,000 and 45,000 MAA MoAb TP39.1, anti-Mr 110,000 MAA MoAb M111, anti-Mr 118,000 MAA MoAb TP36.1, anti-Mr 115,000 MAA MoAb 345.134, anti-ICAM-1 MoAb CL203.4 and anti-Mr 31,000 MAA MoAb M2590, and the cytoplasmic determinants defined by the anti-MAA MoAb 465.12 and 2G-10 display a distribution in uveal melanoma lesions similar to that in cutaneous melanoma lesions. On the other hand, membrane-bound determinants defined by the anti-Mr 100,000 MAA MoAb 376.96, anti-9-O-acetyl-GD3 ganglioside MoAb ME311 and anti-GD2-GD3 ganglioside MoAb ME361 were not detected in the uveal melanoma lesions tested. Furthermore, the membrane-bound determinants defined by the anti-GD3 MoAb R24, anti-nerve growth factor receptor MoAb ME20.4, anti-Mr 97,000 MAA MoAb 140.240, anti-carcinoembryonic antigen MoAb B1.1 and anti-HMW-MAA 149.53, 225.28, and 763.74 have a markedly lower expression in uveal than in cutaneous melanoma lesions. Incubation of uveal melanoma lesions with the pool of the MoAb 149.53, 225.28, and 763.74 recognizing distinct and spatially distant determinants of the HMW-MAA increased the intensity of staining of six lesions and stained four lesions which were not stained by the individual monoclonal antibodies. The distribution of HLA Class I antigens in uveal melanoma lesions resembles that in cutaneous melanoma lesions, since they are expressed in all the lesions of the mixed and epithelioid type but were not detected in those of the spindle type, i.e., the counterparts of nevocellular nevi. HLA Class II antigens are expressed with a lower frequency in uveal than in cutaneous melanoma lesions, since they were detected only in 2 of the 12 lesions. One of them is of the mixed type and the other one of the epithelioid type. Besides HLA antigens the determinants defined by the anti-carcinoembryonic MoAb B1.1, anti-ICAM-1 MoAb CL203.4, and anti-GD3 MoAb R24 displayed a differential distribution in the different histiotypes of uveal melanoma, since they are preferentially expressed in lesions of the mixed and epithelioid type.

摘要

将12个手术切除的葡萄膜黑色素瘤病变与针对14种膜结合和2种细胞质皮肤黑色素瘤相关抗原(MAA)、HLA I类抗原的2个亚基以及HLA - D区域基因产物的单克隆抗体(MoAb)的反应性,与皮肤黑色素瘤病变的反应性进行比较,并与其组织学类型相关联。由抗92,000 Mr和45,000 Mr MAA的MoAb TP39.1、抗110,000 Mr MAA的MoAb M111、抗118,000 Mr MAA的MoAb TP36.1、抗115,000 Mr MAA的MoAb 345.134、抗ICAM - 1的MoAb CL203.4以及抗31,000 Mr MAA的MoAb M2590所定义的膜结合决定簇,以及由抗MAA的MoAb 465.12和2G - 10所定义的细胞质决定簇,在葡萄膜黑色素瘤病变中的分布与在皮肤黑色素瘤病变中的分布相似。另一方面,在测试的葡萄膜黑色素瘤病变中未检测到由抗100,000 Mr MAA的MoAb 376.96、抗9 - O - 乙酰 - GD3神经节苷脂的MoAb ME311以及抗GD2 - GD3神经节苷脂的MoAb ME361所定义的膜结合决定簇。此外,由抗GD3的MoAb R24、抗神经生长因子受体的MoAb ME20.4、抗97,000 Mr MAA的MoAb 140.240、抗癌胚抗原的MoAb B1.1以及抗高分子量MAA 149.53、225.28和763.74所定义的膜结合决定簇在葡萄膜黑色素瘤中的表达明显低于在皮肤黑色素瘤病变中的表达。用识别高分子量MAA不同且空间上相隔较远决定簇的MoAb 149.53、225.28和763.74的混合物孵育葡萄膜黑色素瘤病变,增加了6个病变的染色强度,并使4个未被单个单克隆抗体染色的病变染色。HLA I类抗原在葡萄膜黑色素瘤病变中的分布类似于在皮肤黑色素瘤病变中的分布,因为它们在混合型和上皮样型的所有病变中均有表达,但在梭形型病变中未检测到,梭形型病变即相当于痣细胞痣。HLA II类抗原在葡萄膜黑色素瘤中的表达频率低于在皮肤黑色素瘤病变中的表达频率,因为在12个病变中仅在2个病变中检测到。其中一个是混合型,另一个是上皮样型。除了HLA抗原外,由抗癌胚MoAb B1.1、抗ICAM - 1 MoAb CL203.4和抗GD3 MoAb R24所定义的决定簇在葡萄膜黑色素瘤的不同组织学类型中表现出差异分布,因为它们优先在混合型和上皮样型病变中表达。

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