Abstract
In the treatment of cutaneous melanoma, provisional therapeutic strategies have been designed to combat tumour load using T cells that are sensitized with peptides derived from melanoma autoantigens, such as glycoprotein 100 (gp100), melanoma antigen recognized by T cells 1 (MART-1 or MelanA), tyrosinase and tyrosinase-related protein 1 (TRP-1). We recently found that gp100, MART-1 and tyrosinase are heterogeneously expressed in human cutaneous melanoma (De Vries et al (1997) Cancer Res 57: 3223-3229). Here, we extended our investigations on expression of these immunotherapy candidate proteins to uveal melanoma lesions. Cryostat sections from 11 spindle-type, 21 mixed and epithelioid tumours and four metastasis lesions were stained with antibodies specifically recognizing gp100, MART-1, tyrosinase and TRP-1. In addition, we used the DOPA reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results. High expression of gp100, MART-1 and tyrosinase was found in the uveal melanoma lesions: 80% of the lesions displayed 75-100% positive tumour cells. TRP-1 positivity was slightly less: approximately 65% of the lesions stained in the 75-100% positive tumour cell category. All uveal melanoma lesions were positive for the four markers studied, this being in contrast to cutaneous melanoma where 17% of the advanced primary lesions and metastases were negative. The presence of these antigens was a little lower in metastases. We conclude that uveal melanomas and their metastases express melanocyte-lineage immunotherapy candidate proteins very abundantly. Uveal melanomas differ in this respect from cutaneous melanoma, in which the expression of these immunotherapy antigens was much more heterogeneous. This makes uveal melanoma a suitable candidate tumour for immunotherapeutic approaches.
Highlights
In this paper. we demonstrate the marked expression of these potential targets for immunotherapy in 32 primary uveal melanomas (11 spindle-type: 21 mixed and epithelioid tumours) and in four uveal melanoma metastases
Eleven spindle-type uveal melanomas. 21 mixed and purely epithelioid uveal melanomas and four metastases from uveal melanoma were stained with antibodies against gplOO, MART-1, tyrosinase and tyrosinase-related protein 1 (TRP-1)
Expression of gplOO, MART- I and tyrosinase was very high in both the spindletype melanomas and in the mixed and epithelioid melanomas (Figure 2): 75-100% of tumour cells stained homogeneously strong in approximately 80% of the lesions
Summary
Representatixe tissue samples A-ere freshly received from uveal melanocvtic lesions excised from patients at the Unixersitx Hospital. They were snap frozen in liquid nitrogen and stored at -80°C until 4-pm cryostat sections were cut. Haematoxylin and eosin-stained paraffin sections of these lesions were used for classification. We distinguished two groups of pnmary tumours: 11 were of pure spindle cell type whereas 21 contained epithelioid cells. Tumours with epithelioid cells have a worse prognosis (Gamel et al, 1993). The four metastases were from different patients and were excised from the parotid gland, lymph node, brain and skin
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