Mutation analysis of the Gadd45 gene at exon 4 in atypical fibroxanthoma

Immunohistochemical expression of Bax was analyzed in 7 cases of AFX, and in 7 cases of benign fibrous histiocytoma (BFH) used as a comparison. The expression pattern of Bax was compared to previously reported p53 and Gadd45 expressions in a correspondent series. Mutation of the Gadd45 gene at exon 4 was also analyzed in AFX.AFX and BFH showed immunoreactivities respectively for Bax (3/7, 0/7), Gadd45 (4/7, 1/7) and p53 (2/7, 0/7). There was no exact correlation between p53 expression and Bax or Gadd45 expression. However, the pattern of expression between Bax and Gadd45 was also the same, with the exception of one case. No mutation of the Gadd45 gene at exon 4 was observed in a series of 6 AFX cases where DNA was available (0/6).These results suggest a possible association between Bax and Gadd45 in AFX, and may refute any possibility of dysfunction of Gadd45 in terms of gene mutation, at least at exon 4 of the Gadd45 gene.Atypical fibroxanthoma (AFX) is a nodular ulcerative lesion arising from the sun-exposed skin of the head and neck, typically in the elderly [1,2]. Solar elastosis associated with UV-radiation has been commonly observed in AFX cases [3]. Association between AFX and ultraviolet (UV) radiation has been suspected. On the other hand, in its less common forms with weakened association with UV, AFX occurs on the extremities and the trunk [1,2]. AFX is composed of spindle, plump, epithelioid and bizarre cells, in various proportions, arranged in haphazard, vaguely fascicular or storiform patterns. These histological features of AFX mimic those of high-grade sarcoma, such as malignant fibrous histiocytoma or leiomyosarcoma [2,4], which occurs deep within soft tissue.The tumor-suppressor protein p53 is a transcriptional activator which is involved in cell-cycle control, DNA repair, apoptosis and chromosome/genome instability. UV-induced p53 gene mutations occurring at dipyrimidine sites have been demonstrated in AFX, suggesting a central role for UV radiat