Zamolo Gordana, Coklo Miran, Santini Dusevic Danijela, Kastelan Marija, Batinac Tanja, Materljan Eris, Brumini Gordana
Department of Pathology, Rijeka University School of Medicine, Brace Branchetta 20, 51000 Rijeka, Croatia.
Croat Med J. 2005 Aug;46(4):678-84.
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.
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.
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).
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.
研究p53表达和细胞凋亡在盘状红斑狼疮(DLE)发病机制中是否起作用,以及它们是否与DLE皮损表皮的增殖过度状态和表皮萎缩相关。
共使用70份皮肤活检标本,其中35份为DLE标本,35份为正常标本。采用免疫组织化学法检测蛋白p53和Ki-67的表达。通过末端脱氧核苷酸转移酶(TdT)介导的缺口末端标记法(TUNEL)鉴定凋亡细胞。对DLE苏木精-伊红染色切片进行组织病理学检查,包括分析和评分表皮萎缩及其他组织病理学参数。
DLE中p53表达高于正常皮肤(14.5%对0.6%,P<0.001)。DLE中Ki-67表达也高于正常皮肤(8.0%对3.1%,P<0.001)。两组中p53与Ki-67表达均呈显著正相关(正常皮肤,r=0.46,P<0.009;DLE,r=0.72,P<0.001)。发现Ki-67表达与表皮萎缩程度呈显著负相关(r=-0.75,P<0.001)。Ki-67和p-53表达较高的DLE皮损表皮凋亡程度高于这些分子表达较低时(0-5分制,分别为3.0±1.8对1.6±1.5;P=0.048)。
DLE角质形成细胞中存在p53异常表达,且与角质形成细胞增殖过度和表皮萎缩相关。p53蛋白的积累以及广泛的细胞凋亡表明,p53诱导的凋亡途径激活可能在DLE皮肤病变的发病机制中起作用。