Kageshita T, Nakamura T, Yamada M, Kuriya N, Arao T, Ferrone S
Department of Dermatology, Kumamoto University Medical School, Japan.
Cancer Res. 1991 Mar 15;51(6):1726-32.
The reactivity in an avidin-biotin complex immunoperoxidase reaction with a large panel of anti-human melanoma associated antigen (MAA) and anti-HLA monoclonal antibodies of 24 primary and 11 metastatic acral lentiginous melanoma (ALM) lesions was compared to that of 12 primary and 12 metastatic nodular melanoma (NM) lesions. The expression of the membrane bound vitronectin receptor, Mr 110,000 MAA, Mr 97,000 MAA, and intercellular adhesion molecule-1 was significantly lower in both primary and metastatic ALM lesions than in their NM counterparts. Furthermore, primary ALM lesions displayed a significantly lower expression than primary NM lesions of the membrane bound high molecular weight melanoma associated antigen (HMW-MAA), Mr 110,000 MAA, Mr 100,000 MAA, 9-O-acetyl-GD3, GD2-GD3, and GD2, of the cytoplasmic monoclonal antibody 465.12 defined MAA and of transferrin receptor and of HLA-DQ and DP antigens; ALM metastases expressed a significantly lower level of carcinoembryonic antigen-MAA than NM metastases. These antigenic differences do not reflect an antigenic paucity of ALM cells, since ALM lesions express a higher level of T4-tyrosinase than NM lesions and a level of HLA Class I antigens similar to that of NM lesions. In view of the use of HMW-MAA, Mr 97,000 MAA, and GD3 in immunoscintigraphy and/or in immunotherapy, it is noteworthy that the three antigens are expressed in a similar high percentage of ALM metastases and of primary and metastatic NM lesions, while the HMW-MAA is expressed in a markedly lower percentage of primary ALM lesions than Mr 97,000 MAA and GD3. However, the degree of heterogeneity of HMW-MAA within a positive primary ALM lesion, as measured by the percentage of stained melanoma cells, is lower than that of Mr 97,000 MAA and GD3. The expression of the antigens investigated in ALM and NM lesions was not correlated with the presence of lymphocyte infiltrates, melanin content of melanoma cells, and epithelioid and spindle type of melanoma cells in the lesions. On the other hand, the survival of patients with ALM was inversely correlated with the expression of intercellular adhesion molecule 1 or HMW-MAA in their primary lesions. A potential role of HMW-MAA in the course of the disease is suggested by its significantly higher expression in metastatic than in primary ALM lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
将24例原发性和11例转移性肢端雀斑样痣黑素瘤(ALM)病变与12例原发性和12例转移性结节性黑素瘤(NM)病变,在抗人黑素瘤相关抗原(MAA)和抗HLA单克隆抗体组成的大面板中进行抗生物素蛋白-生物素复合物免疫过氧化物酶反应的反应性比较。原发性和转移性ALM病变中膜结合玻连蛋白受体、分子量110,000的MAA、分子量97,000的MAA和细胞间黏附分子-1的表达均显著低于相应的NM病变。此外,原发性ALM病变中膜结合高分子量黑素瘤相关抗原(HMW-MAA)、分子量110,000的MAA、分子量100,000的MAA、9-O-乙酰-GD3、GD2-GD3、GD2、细胞质单克隆抗体465.12定义的MAA、转铁蛋白受体以及HLA-DQ和DP抗原的表达显著低于原发性NM病变;ALM转移灶中癌胚抗原-MAA的表达水平显著低于NM转移灶。这些抗原差异并不反映ALM细胞的抗原缺乏,因为ALM病变中T4-酪氨酸酶的表达水平高于NM病变,且HLA I类抗原水平与NM病变相似。鉴于HMW-MAA、分子量97,000的MAA和GD3在免疫闪烁显像和/或免疫治疗中的应用,值得注意的是,这三种抗原在ALM转移灶以及原发性和转移性NM病变中的高表达比例相似,而HMW-MAA在原发性ALM病变中的表达比例明显低于分子量97,000的MAA和GD3。然而,通过染色黑素瘤细胞百分比测量,阳性原发性ALM病变中HMW-MAA的异质性程度低于分子量97,000的MAA和GD3。ALM和NM病变中所研究抗原的表达与淋巴细胞浸润的存在、黑素瘤细胞的黑色素含量以及病变中黑素瘤细胞的上皮样和梭形类型均无相关性。另一方面,ALM患者的生存率与其原发性病变中细胞间黏附分子1或HMW-MAA的表达呈负相关。HMW-MAA在转移性ALM病变中的表达显著高于原发性病变,提示其在疾病进程中可能发挥潜在作用。(摘要截断于400字)