Glutathione-S-transferase pi expression in toxic epidermal necrolysis: a marker of putative oxidative stress in keratinocytes.
BACKGROUND
Toxic epidermal necrolysis (TEN) is a dramatic drug-induced emergency related to extensive destruction of the epidermis. There is evidence that its pathomechanism involves impaired detoxication of xenobiotics. Glutathione-S-transferase pi (GST-pi) is a phase II detoxifying enzyme involved in drug metabolization by human keratinocytes.


METHODS
Immunohistochemistry was performed in order to assess the expression of GST-pi in keratinocytes of TEN, other cutaneous adverse drug reactions and bullous pemphigoid.


RESULTS
GST-pi was disclosed in the involved epidermis of 16/16 TEN patients. It was present in the cytoplasm of suprabasal keratinocytes. GST-pi was also expressed in the clinically uninvolved skin in a majority (8/12) of TEN patients. By contrast, it was rarely and poorly expressed in the other tested dermatoses.


CONCLUSIONS
The pathomechanism of TEN is not related to an impaired quantitative expression of GST-pi. GST-pi expression is an early event in TEN. As oxidative stress is a major inducer of GST-pi, this mechanism might be involved in TEN. Its GST-pi expression mainly restricted to the suprabasal keratinocytes suggests that the pathomechanisms leading to keratinocyte death in TEN are distinct at different levels of the epidermis.
Paquet
P
P
Department of Dermatopathology, University of Liège, Liège, Belgium. P.Paquet@chu.ulg.ac.be
Piérard
G E
GE
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010391:Pemphigoid, Bullous / Q000201:enzymology; D013262:Stevens-Johnson Syndrome / Q000201:enzymology*
D015415:Biomarkers; D051549:Glutathione S-Transferase pi