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Herceptin-therapy in Uveal and Conjunctival Melanoma and in Basal Cell Carcinomas of the Eyelid is not indicated

1Stiemer R. H., 2Vogel U., 1Zierhut M., 1Rohrbach J. M., 2Bültmann B.,
1Eberhard-Karls-Universität Tübingen, Universitäts-Augenklinik, Abt. I (Tübingen)
2Universität Tübingen, Institut für Pathologie (Tübingen)

Purpose: Since the approval of Herceptin®, the promising new therapeutic monoclonal antibody against the external domain of the growth factor receptor HER2/c-erbB2, for therapy in breast cancer, it is of interest whether it can be applied to the therapy of other malignant tumors. However, a strong expression of HER2 on the surface of the tumor cells as well as HLA-A2 of the patient is a prerequisite for the Herceptin® therapy. Therefore, we studied the expression and the genomic status of HER2 in uveal and conjunctival melanoma and in basal cell carcinoma of the eye lid. Additionally we have performed HLA class I and class II typing of patients with basal cell carcinoma of the eye lid and the skin.
Method: Specimens from uveal melanoma (n=5), conjunctival melanoma (n=5) and basal cell carcinoma (n=5), respectively, were fixed in neutral buffered 4% formalin and embedded in paraffin. To assess the immunohistochemical and genomic status of HER2 we used the Dako polyclonal antibody A0485 for immunohistochemistry and the PathVysion-kit (Vysis) for fluorescence in situ hybridization. Immunostaining was scored according to the criteria of the Hercep-Test from Dako. The fluorescence in situ hybridization was evaluated according to the guidelines from Vysis. HLA class I and class II typing was performed on the DNA level isolated from peripheral lymphocytes derived from patients with basal cell carcinoma of the eyelid (n=20) and of the skin (n=10).
Results: No tumor showed a positive expression of HER2. Moreover, the tumor cells displayed a normal genomic status with 2 signals for chromosome 17 and 2 signals for HER2. HLA class I and class II expression was not correlating with the appearance of basal cell carcinoma of the eyelid and the skin.
Conclusions: Herceptin does not seem to be applicable to the therapy of uveal and conjunctival melanoma and basal cell carcinoma of the eye lid.