Title: Mutation Analysis of the Gadd45 Gene at Exon 4 in Atypical Fibroxanthoma

Background: Atypical fibroxanthoma (AFX) histologically mimics high-grade sarcoma in the skin, although it follows a benign clinical course. AFX occurs in the sun-exposed skin ands for this reason, an association with ultraviolet light has long been suspected. Methods: Bax is a programmed cell death protein and belongs to the Bcl-2 family. The immunohistochemical expression of Bax was analyzed in 7 cases of AFX, and in 7 cases of benign fibrous histiocytoma (BFH) used as a comparison. Gadd45 is a multifunctional DNA damage-inducible gene associated with the process of DNA damage. Mutation of the Gadd45 gene in exon 4 was also analyzed in AFX. Results: AFX and BFH showed immunoreactivities respectively for Bax (3/7, 0/7) and Gadd45 (4/7, 1/7). The pattern of expression between Bax and Gadd45 was also the same except for one case, in which no mutation of the Gadd45 gene in exon 4 was observed in a series of 6 AFX cases where DNA was available (0/6). Conclusion: This result suggests possible association between Bax and Gadd45, and may refuse any possibility of dysfunction of Gadd45 in terms of gene mutation, at least at exon4 of the Gadd45 gene. Revised manuscript: Abstract