Expression of p53 and apoptosis in discoid lupus erythematosus.
OBJECTIVE
To investigate whether p53 expression and apoptosis play a role in the pathogenesis of discoid lupus erythematosus (DLE) and whether they are associated with a hyperproliferative state in the epidermis of DLE lesions and epidermal atrophy.


METHODS
A total of 70 skin biopsy specimens, 35 DLE and 35 normal, were used. Expression of protein p53 and Ki-67 was examined immunohistochemically. Apoptotic cells were identified by terminal deoxynucleotidyl transferase (TdT)-mediated nick end labeling (TUNEL). Histopathological examination of hematoxylin-eosin-stained sections of DLE included analysis and scoring of epidermal atrophy and other histopathological parameters.


RESULTS
p53 expression was greater in DLE than in normal skin (14.5 vs 0.6%, P<0.001). Ki-67 expression was also greater in DLE than in normal skin (8.0 vs 3.1%, P<0.001). A significant positive correlation between p53 and Ki-67 expression was found in both groups (normal skin, r=0.46, P<0.009; DLE, r=0.72, P<0.001). A significant negative correlation (r=-0.75, P<0.001) between Ki-67 expression and the intensity of epidermal atrophy was found. The degree of apoptosis in the epidermis of DLE lesions with higher Ki-67 and p-53 expression was higher than when the expression of these molecules was low (3.0+/-1.8 vs 1.6+/-1.5 on a scale from 0-5; P=0.048).


CONCLUSIONS
Aberrant p53 expression occurs in the keratinocytes of DLE and is associated with keratinocyte hyperproliferation and epidermal atrophy. Accumulation of p53 protein, together with an extensive apoptosis, suggests that the activation of a p53-induced apoptotic pathway may play a role in the pathogenesis of skin lesions in DLE.
Zamolo
Gordana
G
Department of Pathology, Rijeka University School of Medicine, Brace Branchetta 20, 51000 Rijeka, Croatia. gordanazamolo@yahoo.com
Coklo
Miran
M
Santini Dusevic
Danijela
D
Kastelan
Marija
M
Batinac
Tanja
T
Materljan
Eris
E
Brumini
Gordana
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D001706:Biopsy; D005260:Female; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics*; D008297:Male; D008875:Middle Aged