Bodey B, Kaiser H E, Goldfarb R H
Department of Pathology, School of Medicine, University of Southern California, Los Angeles, USA.
Anticancer Res. 1996 Jan-Feb;16(1):517-31.
During a systematic, immunocytochemical screening of 40 human cutaneous melanomas (30 primary and 10 metastatic) for immunophenotype (IP) heterogeneity, we employed a library of 20 well characterized, commercially available mono- and polyclonal antibodies. The use of the sensitive, indirect, four to six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent results. The immunocytochemically most characteristic IP for primary cutaneous melanoma, as detected by us was: HMB45+, S-100+, CEA+, vimentin+, cytokeratin 19+, p53+, Rbgene+, nm23+, HLA-DR+, HL.A-DP+, c-erbB3/HER-3+/-, cytokeratin 10/13+/-, HLA-DQ-, cytokeratin 5/8-, EMA-, c-myc-, and actin-. During melanoma progression, a tendency toward poor differentiation (dedifferentiation) and an increase in c-myc expression have both been observed, the latter downregulating HLA-A,B,C expression and consequently diminishing the possibility of melanoma cell Iysis by powerful CD8+, cytotoxic T lymphocytes (CTL) or other cytotoxic cells which requires HLA class I antigens. The development of the metastatic potential in melanomas caused an increase in CEA expression, eliminated the presence of nm23, and prompted the appearance of actin among the intermediate filaments, composing the cytoskeleton of these malignant tumor cells. The most characteristic IP for MMs, identified by this study was HMB45+, S-100+, CEA+, EMA+, vimentin+, HLA-DR+, HLA-DP+, cytokeratin 19+, actin-, c-erbB3/HER-3+, p53+, cytokeratin 10/13+/-, c-myc+/-, c-erbB2/HER-2+/-, HLA-DQ-, cytokeratin 5/8-, Rb gene-, nm23-. It has been observed that adhesion molecules and integrins play a significant role in the complex process of melanoma metastasis and thus we propose a blocking of these de novo expressed molecules with the appropriate antibodies as a form of immunotherapy of PMs and early stages of MMs.
在对40例人类皮肤黑色素瘤（30例原发性和10例转移性）进行免疫表型（IP）异质性的系统免疫细胞化学筛查过程中，我们使用了一个包含20种特征明确的市售单克隆和多克隆抗体的文库。采用灵敏的间接四至六步免疫过氧化物酶或碱性磷酸酶偶联链霉亲和素 - 生物素抗原检测技术，取得了优异的结果。我们检测到的原发性皮肤黑色素瘤在免疫细胞化学方面最具特征性的IP为：HMB45 +、S - 100 +、CEA +、波形蛋白 +、细胞角蛋白19 +、p53 +、Rb基因 +、nm23 +、HLA - DR +、HL.A - DP +、c - erbB3/HER - 3 +/ -、细胞角蛋白10/13 +/ -、HLA - DQ -、细胞角蛋白5/8 -、EMA -、c - myc -、肌动蛋白 -。在黑色素瘤进展过程中，已观察到分化不良（去分化）的趋势和c - myc表达的增加，后者下调HLA - A、B、C的表达，从而降低了黑色素瘤细胞被强大的CD8 + 细胞毒性T淋巴细胞（CTL）或其他需要HLA I类抗原的细胞毒性细胞裂解的可能性。黑色素瘤转移潜能的发展导致CEA表达增加，nm23消失，并促使构成这些恶性肿瘤细胞细胞骨架的中间丝中出现肌动蛋白。本研究确定的转移性黑色素瘤最具特征性的IP为：HMB45 +、S - 100 +、CEA +、EMA +、波形蛋白 +、HLA - DR +、HLA - DP +、细胞角蛋白19 +、肌动蛋白 -、c - erbB3/HER - 3 +、p53 +、细胞角蛋白10/13 +/ -、c - myc +/ -、c - erbB2/HER - 2 +/ -、HLA - DQ -、细胞角蛋白5/8 -、Rb基因 -、nm23 -。已经观察到黏附分子和整合素在黑色素瘤转移的复杂过程中起重要作用，因此我们建议用适当的抗体阻断这些新表达的分子，作为原发性黑色素瘤和转移性黑色素瘤早期免疫治疗的一种形式。
