Expression of Bcl-2 family proteins in psoriasis.
OBJECTIVE
To elucidate the mechanisms involved in apoptosis of psoriatic keratinocytes by examining the expression of pro-apoptotic (Bak, Bax) and anti-apoptotic (Bcl-2, Bcl-X) Bcl-2 family of proteins, as well as the expression of p53 and Ki-67 proteins in normal skin, and uninvolved and involved psoriatic skin.


METHODS
A total of 90 skin samples (30 cases of involved and uninvolved psoriatic skin and normal skin) were examined immunohistochemically to determine the protein expression of p53, Ki-67, Bcl-2, Bcl-X, Bax, and Bak. The results were quantified and expressed as a percentage of positive keratinocytes.


RESULTS
There was a significant increase in Ki-67 (17.05 vs 3.65; P<0.001), Bcl-X (40.21 vs 13.97; P<0.001), Bak (89.46 vs 73.36; P<0.001), and Bax (50.00 vs 29.25; P<0.001) expression and a decrease in Bcl-2 (3.23 vs 6.25; P=0.008) expression in involved psoriatic skin, as well as an increase in Bcl-X (25.13 vs 13.97; P<0.001) expression in uninvolved psoriatic skin, when compared to normal skin. Samples with higher percentage of Ki-67 positive cells showed a higher percentage of p53 positive cells (correlation coefficient r=0.75 in involved psoriatic samples, P<0.001; r=0.88 in uninvolved psoriatic samples, P<0.001; and r=0.85 in normal skin samples, P<0.001). Samples with higher percentage of p53 positive cells expressed pro-apoptotic Bak and Bax in higher percentage of cells; the correlation coefficients were r=0.74 and r=0.68 in involved psoriatic samples (P<0.001 for both), r=0.75 and r=0.69 in uninvolved psoriatic samples (P<0.001, for both), and r=0.87 and r=0.70 in normal skin samples (P<0.001, for both).


CONCLUSIONS
Increased expression of Bcl-X protein was associated with psoriatic epidermal hyperplasia. Strong Bax and Bak expression in involved psoriatic skin are probably inhibitory mechanisms counteracting intensive proliferation.
Batinac
Tanja
T
Department of Dermatovenerology, University Hospital Rijeka, Rijeka, Croatia.
Zamolo
Gordana
G
Hadzisejdić
Ita
I
Zauhar
Gordana
G
Brumini
Gordana
G
Ruzić
Alen
A
Persić
Viktor
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494772:BAK1 protein, human; C494826:BAX protein, human; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein