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

Akio Sakamoto,Yukihide Iwamoto,Masazumi Tsuneyoshi,Yoshinao Oda,Shizuka Akieda

doi:10.1186/1471-5945-9-1

Abstract

BackgroundAtypical fibroxanthoma (AFX) histologically mimics high-grade sarcoma in the skin, although it follows a benign clinical course. AFX occurs in the sun-exposed skin and for this reason, an association with ultraviolet light has long been suspected. Bax and Gadd45 are p53 effector proteins. Bax is a programmed cell death protein and belongs to the Bcl-2 family. Gadd45 is a multifunctional DNA damage-inducible gene associated with the process of DNA damage.MethodsImmunohistochemical 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.ResultsAFX 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).ConclusionThese 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.

Highlights

Atypical fibroxanthoma (AFX) histologically mimics high-grade sarcoma in the skin, it follows a benign clinical course
UVinduced p53 gene mutations occurring at dipyrimidine sites have been demonstrated in AFX, suggesting a central role for UV radiation in the pathogenesis of AFX [5,17]. p53 protein is a key regulator for cell-cycle arrest and apoptosis induced by DNA damage [21]
These associations of Bax and Gadd45 noted in AFX may be consistent with p53 effector upregulation against UV radiation, there seemed to be no correlation between p53 expression, and the expression of Bax or Gadd45

Summary

Introduction

Atypical fibroxanthoma (AFX) histologically mimics high-grade sarcoma in the skin, it follows a benign clinical course. AFX occurs in the sun-exposed skin and for this reason, an association with ultraviolet light has long been suspected. Bax and Gadd are p53 effector proteins. 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]. Association between AFX and ultraviolet (UV) radiation has been suspected. AFX is composed of spindle, plump, epithelioid and bizarre cells, in various proportions, arranged in haphazard, vaguely fascicular or storiform patterns. These histological (page number not for citation purposes)

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