Regulatory T-cell cytokines in patients with nonsegmental vitiligo.

In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor-ß (TGF-ß) and interleukin-10 (IL-10), associated with regulatory T-cells (Treg) is not completely known. In this study, the role of Treg-cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls. All samples were evaluated staining for forkhead box P3 (Foxp3), TGF-ß, and IL-10 using the standardized streptavidin-biotin immunoperoxidase immunohistochemistry method. Foxp3 expression was lower in lesional vitiligo skin specimens compared to controls; it was also lower in lesional vitiligo specimens than nonlesional vitiligo specimens. IL-10 levels were lower in lesional vitiligo specimens compared to the controls, whereas IL-10 expression was significantly lower in lesional specimens compared with nonlesional specimens. TGF-ß expression was higher in both lesional and nonlesional skin specimens of patients with vitiligo compared to controls. TGF-ß expression was lower in lesional skin specimens than nonlesional skin specimens. In addition, there was no significant correlation between Foxp3 expression with TGF-ß and IL-10 expressions in lesional skin specimens in the vitiligo group. In this study, results supporting the contribution of Treg cells and IL-10 deficiency to the autoimmune process were obtained. Therefore, future studies are necessary to demonstrate the definitive role of Treg-cell functions in the etiopathogenesis of vitiligo.

Metastasis suppressor proteins in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research.

Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma.

BACKGROUND: Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. METHODS: A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. RESULTS: NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. CONCLUSION: The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors.

Detection of human herpesvirus 7 in pityriasis rosea by nested PCR.

BACKGROUND: Clinical presentation, immunologic, light microscopic, and electron microscopic studies suggest a viral etiology for pityriasis rosea (PR). OBJECTIVE: To evaluate whether human herpesvirus 7 (HHV-7) is an etiologic factor for PR. PATIENTS AND METHODS: Twenty-one PR patients (12 female, nine male) aged between 12 and 52 years, whose diagnoses were confirmed clinically and histopathologically, were included in the study. The duration of the disease was questioned. Tissue samples of 5-mm punch biopsy material were collected from the patients and from six healthy volunteers (three female, three male) as the controls. Nested polymerase chain reaction (PCR) with specific primers for HHV-7 DNA sequences (OPERON technologies Inc., HV-7S/HV-8A external sences and HV-10S/HV11A internal sences) was performed on each tissue sample. Polymerase chain reaction products were analyzed by electrophoresis on 2% agarose gels. After molecular weight markers (Haphi174) had been placed and visualized on an ultraviolet transilluminator, the gels were immersed and photographs were taken. RESULTS: The mean age was 29.86 +/- 11.77 for the PR patients and 25.33 +/- 11.69 for the controls. The mean duration of the disease was 16.28 +/- 15.74 days. Human herpesvirus 7 DNA sequences were detected in six of the PR patients (28.57%). The mean duration of the disease was calculated as 11.67 +/- 9.85 for the HHV-7-positive patients (patient nos. 3, 4, 5, 7, 8, 9) and 18.13 +/- 17.05 for the HHV-7-negative patients, and there was no statistically significant differences in either of the groups (U = 29.5, W = 50.5, P = 0.2241, using the Mann-Whitney U and Wilcoxon's rank sum W-tests). Nested PCR was negative for HHV-7 in all of the specimens from the controls. There was no statistically significant difference for the presence of HHV-7 DNA sequence between the PR patients and the controls (P = 0.2843, Fisher's exact two-tail analysis test). CONCLUSION: Our results failed to support a possible role for HHV-7 in the pathogenesis of PR.