Expression of gp100, MART-I, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group

With the recent availability of novel antibodies against melanoma antigens tyrosinase and MART-I, it is important to validate their usefulness in path ology practice and in screening patients for immunotherapy treatment. In th e present study conducted by the Melanoma Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC-MCG), immunohisto chemical staining for gp100 (antibodies NKI-beteb and HMB-45), MART-1 (A103 ), tyrosinase (T311), and S100 (S100) was compared on formalin-fixed and pa raffin-embedded tumour lesions from 80 patients with 130 malignant melanoma lesions, comprising 44 primary tumours, 18 locoregional metastases, 41 lym ph node metastases, and 27 visceral metastases from the lung, liver, and br ain. A score between 0 and 5 was allocated to each immunohistochemically st ained section. These scores were evaluated in a statistical analysis. S100 was by far the most sensitive marker in all four types of lesions tested. A part from a significantly better performance for T311 in primary melanomas compared with HMB-45, no significant differences were observed between the four remaining antigens tested. Three settings were next investigated to de termine whether the expression of melanoma antigens decreases with tumour p rogression. First, within the primary melanomas, only NKI-beteb and A103 st aining showed a nearly significant negative correlation with Clark's level of invasion and a similar tendency was observed for these antibodies with B reslow thickness. Second, when comparing primary melanoma-metastasis pairs from the same patient, lymph node metastases showed less staining with NKI- beteb, HMB-45, A103, and T311, at a level near significance. This differenc e was not significant when comparing the primary tumour with visceral metas tases, probably due to the lower numbers of pairs. Third, regarding tumour progression from primary melanoma to locoregional, to lymph node, to viscer al metastasis, a significant decrease with progression was found only for T 311, The apparently stable expression of most of the melanoma antigens, and the small contribution of decreased expression in melanoma tumour progress ion, supports the rationale for immunotherapy based on the melanoma immunog ens gp100, MART-1, and tyrosinase. Copyright (C) 2000 John Wiley & Sons, Lt d.