Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2 alpha in cutaneous melanoma

The loss of transcription factor AP-2 alpha expression has been shown to as sociate with tumourigenicity of melanoma cell lines and poor prognosis in p rimary cutaneous melanoma. Altogether these findings suggest that the gene encoding AP-2 alpha (TFAP2A) acts as a tumour suppressor in melanoma. To le arn more of AP-2 alpha's down-regulation mechanisms, we compared the immuno histochemical AP-2 alpha protein expression patterns with the corresponding mRNA expression detected by in situ hybridization in 52 primary melanomas. Of the 25 samples with AP-2 alpha protein negative areas, 16 (64%) express ed mRNA throughout the consecutive section. Nine specimens (36%) contained equally mRNA- and protein-negative areas, suggesting that the loss of AP-2 alpha protein associated with lack of the mRNA transcript. The highly AP-2 alpha protein-positive tumours (n = 27) were concordantly mRNA positive in 25 (92.6%) cases. Thirteen primary tumours were further analysed using micr osatellite markers D6S470 and D6S263 for loss of heterozygosity (LOH) of a locus harbouring TFAP2A. LOHs or chromosome 6 monosomy were found in four o ut of five (80%) informative AP-2 alpha mRNA- and protein-negative tumour a reas, but also within five out of 13 (38%) informative AP-2 alpha mRNA-posi tive tumour areas. This chromosome region is thus suggestive of harbouring a putative tumour suppressor gene of cutaneous melanoma, but this referring specifically to TFAP2A could not be completely verified in this analysis. We conclude that a failure in post-transcriptional processing of AP-2 alpha is a possible inactivation mechanism of AP-2 alpha in cutaneous melanoma. (C) 2000 Cancer Research Campaign.