Psoriasis is a hyperproliferative inflammatory skin disease; therefore, it is highly likely that psoriatic skin lesions may transform into malignancies. However, malignant transformation is not common. We performed immunohistochemical studies using anti-cyclin D1, anti-cyclin E, anti-pRb, anti-p53, anti-p16INK4a, and anti-Ki-67 antibodies in normal skin, psoriatic epidermal tissue, and squamous cell carcinoma (SCC) tissue. Furthermore, western blot analysis and immunohistochemical staining were performed to ascertain differences in cyclin D1, cyclin E, pRb, and Ki-67 expression before and after treatment for psoriasis. Cyclin D1 expression was higher in chronic psoriatic lesions than that in normal epidermis. Psoriasis lesions showed a strong intensity of positive nuclear staining for cyclin D1 among several normally stained nuclei in the basal layer. Cyclin E expression in psoriasis was stronger in the granular and spinous layer than in the normal epidermis. Expression levels of pRb and p53 were found to be higher in the psoriasis group compared with the normal epidermis. Total basal layer cell counts for p53WT expression were found to be significantly higher in the psoriasis group compared with the normal group. However, p16 expression was very weak in the normal and psoriasis groups compared with that in the SCC group. Ki-67 immunoreactivity was significantly higher in psoriasis compared with normal epidermis and was similar with that in the SCC group. According to immunohistochemistry and immunoblot analysis, the expression levels of cyclin D1, cyclin E, pRb, and Ki-67 in psoriasis lesions decreased after treatment and were similar with those in the normal group. Thus, increased expression of cyclin D1 and cyclin E may be involved in cell cycle progression in psoriatic epidermis, and pRb and p53 may play important roles in the prevention of malignant transformation under the hyperproliferative state in psoriasis.
Abstract. Psoriasis is a chronic inflammatory skin disease, characterized by a combination of abnormal proliferation of keratinocytes, immunology and vascular proliferation. Proteomic analyses have revealed some clues regarding the pathogenesis of psoriasis. In the present study, we conducted an investigation of different proteomes of psoriatic lesional skin, and compared them with those of normal and nonlesional psoriatic skin. We performed 2-D gel electrophoresis, liquid chromatography tandem mass spectrometry (LC-MS/ MS) analysis and database searches. Expression of proteins were evaluated by immunoblot and immunohistochemistry analyses. Our data showed differential expression of 74 and 145 protein spots in non-lesional and lesional psoriatic skin, respectively. Eleven of 36 proteins, which were identified by LC-MS/MS, were categorized as apoptosis-regulating proteins. Other protein spots were categorized as proteins with involvement in the negative regulation of apoptosis, defense response-related proteins and inflammatory response. Of particular interest, increased expression of glutathione S transferase 1 (GSTP1) and peroxiredoxin 2 (PRDX2), which are involved in the Redox balance system, and SFN, which is involved in the cellular proliferation system, was observed in psoriatic lesional skin. Localization of GSTP1 and SFN was observed above the middle layer of the epidermis in psoriatic skin lesions. Expression of PRDX2 was clearly observed below the middle layer of the epidermis in chronic type psoriatic skin lesions. Taken together, 36 identified proteins were associated with biological regulation, including regulation of cell death, defense response, inflammatory response and reactive oxygen species (ROS) regulation. PRDX2 and GSTP1 may play roles in compensating mechanisms for reduction of ROS stress, and SFN may play roles in prevention of cancer development in proliferating cells through G2/M cell cycle arrest upon accidental DNA damage within psoriatic skin lesions.
A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.
PurposeQuestionnaire-based diagnostic criteria for atopic dermatitis (AD) have been proposed to detect the major group of AD with flexural dermatitis. We aimed to develop novel, questionnaire-based diagnostic criteria for childhood AD, which can detect more comprehensive AD including non-flexural type.MethodsThe draft version of questionnaire to detect childhood AD was prepared to be used for preliminary hospital- (n=1,756) and community-based (n=1,320) surveys. From analysis, the Reliable Estimation of Atopic dermatitis of ChildHood (REACH) was derived and verified in derivation (n=1,129) and validation (n=1,191) sets by community-based surveys.ResultsThe REACH consists of 11 questions including 2 major and 9 minor criteria. AD is diagnosed as the major group of 'eczema on the antecubital or popliteal fossa' to fulfill the 2 major criteria (2M), and the minor group of 'eczema on the non-antecubital or popliteal fossa' to fulfill the 1 major plus 4 or more minor criteria (1M+4m). In the validation set, the overall 1-year AD prevalence by the REACH was estimated as 12.3% (95% CI, 10.5%-14.2%), and the REACH showed a sensitivity of 75.2%, a specificity of 96.1%, and an error rate of 6.4%. The REACH demonstrated better diagnostic performance than the ISAAC in terms of the number of misclassification (10.0%).ConclusionsWe propose the REACH as new full, questionnaire-based diagnostic criteria for childhood AD in epidemiological surveys. Further studies are warranted to validate the REACH in different populations or countries in the context of large-scale, epidemiological surveys.
BackgroundIt is important to educate families of pediatric patients with atopic dermatitis (AD) so that they have a correct understanding of AD.ObjectiveThe purpose of this study is to introduce, evaluate, and improve our family-engaged educational program.MethodsChildren suffering from AD and their families have participated in a half-day educational program called "AD school" with catchy slogans such as "Enjoy with AD Families!" every year since 2005. Educational lectures were conducted for parents. For children with AD, various entertaining programs were provided. A feedback survey about AD school was administered for the purpose of evaluation.ResultsA total of 827 people (376 patients and 451 family members) participated in this program over 7 years. On-site surveys showed a positive response (i.e., "excellent" or "good") for the prick test (95.1%), emollient education (78.4%), educational lecture (97.0%), drawing contest and games (90.2%), and recreation (magic show; 99.0%) respectively. Telephone surveys one year later also elicited a positive response.ConclusionWe herein introduce the experience of a half-day, family-engaged educational program for AD. Family-engaged education programs for AD such as this AD school encourage and validate family participation in the treatment of their children's AD.
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