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 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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Sakamoto
Akio
A
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. akio@med.kyushu-u.ac.jp
Akieda
Shizuka
S
Oda
Yoshinao
Y
Iwamoto
Yukihide
Y
Tsuneyoshi
Masazumi
M
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D051028:bcl-2-Associated X Protein; C439070:GADD45A protein, human; D000097642:GADD45 Proteins