The pathogenesis of juvenile angiofibroma (JA) remains unsolved. Further, it is unknown whether this fibrovascular tumour arises from the endothelial or stromal cells. Comparative genomic hybridisation analysis of these tumours revealed deletions of chromosome 17, including regions for the tumour suppressor gene p53 as well as the Her-2/neu oncogene, which are altered in many human tumours. In order to analyse if they are also important for progression of JA, the p53 gene and Her-2/neu gene were evaluated in 7 tumours by two-colour in situ hybridisation analysis using probes for the centromer of chromosome 17 either with a specific probe against p53 or Her-2/neu. In 5 out of 7 JAs, gene losses were detected for both genes ranging from 10.5 to 31.5%, respectively. Gene amplifications were not observed. Semi-quantitative RT-PCR analysis from laser microdissected single endothelial cells and fibroblasts showed up-regulated p53 mRNA levels in 4 out of the 7 JAs analysed in both investigated cell types and in one case in only endothelial cells. Her-2/neu mRNA was noted to be up-regulated in 2 JAs and down-regulated in 1 JA for both cell types. Western blot analysis as well as immunohistochemistry detected no p53 protein in the 5 investigated JAs, indicating absence of mutated p53. Our findings indicate that chromosomal losses on chromosome 17 imply p53 gene and Her-2/neu gene losses in JAs. However, comparison of p53 and Her-2/neu mRNA levels in laser microdissected endothelial and stromal cells were not conclusive to answer the question of the tumour cell of origin in JA.

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