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• Serum squamous cell antigen (SCCA)-2 was significantly increased in pediatric atopic dermatitis (AD) in Ishigaki cohort. • Low disease prevalence and mild disease severity are known in Ishigaki cohort presumably due to the moisturizing subtropical climate. • Serum SCCA2 was associated with clinical disease severity, and demonstrated a good diagnosability in pediatric AD even in such Ishigaki cohort. We sometimes encounter difficulties in assessing the severity of pediatric atopic dermatitis (AD) using currently available biomarkers such as thymus and activation-regulated chemokine (TARC) due to the higher baseline values in non-AD children. Recent case control studies have indicated the usefulness of squamous cell carcinoma antigens (SCCAs) in pediatric and adult AD. Notably, SCCAs are induced by IL-4 and IL-13, vital Th2 cytokines that play important roles in AD etiology. Relatively low prevalence and mild disease severity of pediatric AD are observed in our Ishigaki cohort presumably due to the moisturising subtropical climate, which could conversely mean possible higher allergic potential of non-AD subjects towards AD. Thus, the purpose of this study was to further investigate the feasibility of using SCCAs together with TARC and periostin as biomarkers for pediatric AD even in the Ishigaki cohort. We enrolled 1459 nursery school children and identified 96 as having AD through 2009–2011. As statistical analyses, we performed Student's t -test, correlation analysis, and receiver and operating characteristic (ROC) analysis. Serum SCCA1, SCCA2, periostin and TARC levels were all significantly increased in AD compared with those in non-AD, but only serum SCCA2 showed a significant increase in AD when assessed in each age group or in subgroup analysis. Among the biomarkers tested, serum SCCA2 also showed the best correlations with clinical AD severity and TARC and showed the best diagnosability for AD in ROC analysis. SCCA2 is a potent biomarker for pediatric AD in the Ishigaki cohort. [ABSTRACT FROM AUTHOR]

Background The contribution of the E-cadherin transcriptional repressors Snail and Slug to invasion and metastasis has strengthened the evidence for the importance of epithelial-mesenchymal transition ( EMT) in carcinoma progression. However, to the best of our knowledge, no study has described the immunohistochemical staining of the EMT-related proteins Snail/Slug in skin tumors and the correlation between Snail/Slug and tumor suppressor p53/p63. Methods We performed immunohistological staining of Snail, Slug, E-cadherin, p53 and p63 in 20 archived specimens each of seborrheic keratosis ( SK), actinic keratosis ( AK) and squamous cell carcinoma in situ ( SCCIS), and 53 specimens of cutaneous squamous cell carcinomas ( SCC). Fifteen normal skin ( NS) specimens served as controls. Results Significant negative correlations were observed between Snail and E-cadherin expression and between Slug and E-cadherin expression (Snail: R2 = 0.5432, p < 0.01; Slug: R2 = 0.4666, p < 0.01). Conclusions The staining intensities of Snail and Slug are associated with decreased E-cadherin staining in SCC and this may promote EMT. However, the staining intensities of p53 and p63 are not significantly correlated with the loss of E-cadherin. [ABSTRACT FROM AUTHOR]

Background: It has become evident that resident stromal cells, such as fibroblasts and inflammatory cells, are involved in the metastatic process, including proliferation or migration of malignant neoplasms. We analyzed CD10+ stromal cells, dermal macrophages and Langerhans cells (LCs) in skin tumors. Methods: Immunohistological staining was performed with markers for macrophages (CD68), LC (CD1a), stromal fibroblasts (CD10) and cell proliferation (Ki67) in 12 normal skins (NSs) and 15 cases each of seborrheic keratosis (SK), actinic keratosis (AK), keratoacanthoma (KA), Bowen’s disease (BD) and squamous cell carcinoma (SCC). Results: All SCCs showed weak to strong stromal CD10 expression, while all NS, SK and AK were negative. Weak CD10 expression was observed in only 2 of 15 samples in both BD and KA. The number of CD68+ cells and Ki67 labeling index in SCC and BD were significantly higher than that in KA, AK and SK. In contrast, the number of LC was lower in SCC and BD. The stromal CD10 expression was significantly correlated with the Ki67 labeling indices and CD68+ cells and negatively correlated with decreased LC. Conclusions: The stromal CD10 expression is associated with malignant transformation of keratinocytes together with infiltration of dermal macrophages and loss of LC. [ABSTRACT FROM AUTHOR]

Background The entire minichromosome maintenance (MCM) family (MCM2–7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. Objectives To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). Methods Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. Conclusions Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify the role of Bcl-2 protein and adrenomedullin (AM) expression in relation to apoptosis in the neoplastic changes of squamous epithelium of the uterine cervix. Methods: Apoptosis in sections of normal cervical epithelium, cervical intraepithelial neoplasia (CIN), and invasive squamous cell carcinoma was determined by terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL) assay. Bcl-2 protein and AM expression were analyzed using the avidin-biotin immunoperoxidase method. Results: On the basis of the TUNEL assay, the apoptosis positive rate of the nuclei in early invasive squamous carcinoma and in bulky invasive squamous carcinoma was significantly higher than that in normal cervical epithelium, but no such increase in the apoptosis-positive rate was noted in the nuclei in CIN. Immunohistochemical staining revealed that Bcl-2 protein and AM were immunolocalized in the cytoplasm of invasive squamous carcinoma cells, but not in either CIN lesions or normal cervical epithelium. Bcl-2 protein expression was more prominent in bulky invasive squamous carcinoma cells than in early invasive squamous carcinoma cells. AM expression was also more abundant in bulky invasive squamous carcinoma compared with that in early invasive squamous carcinoma. Conclusion: The present results suggest that the expression of Bcl-2 protein and AM in invasive squamous carcinoma may play crucial roles in selecting carcinoma cells resistant to apoptosis and in promoting malignant progression. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cathepsin K (CTSK), a cysteine protease with strong collagenolytic properties, is involved in extracellular matrix turnover. In the previous studies, CTSK expression was detected in peritumoral fibroblasts (Fbs) around squamous cell carcinoma (SCC), but not in those surrounding benign epidermal tumors. However, the mechanism governing CTSK expression in epidermal tumors remains unclear. Objective: To study the regulatory mechanisms of fibroblastic CTSK expression in the SCC–stromal interaction. Methods: We examined dynamic interactions of Fbs with tumorigenic SCC cells (A431 and A253) or normal human keratinocytes. Results: SCC cells and normal keratinocytes did not synthesize CTSK, while Fbs constitutively expressed CTSK. When cocultured, SCC cells upregulated fibroblastic CTSK expression more potently than did normal keratinocytes, which was mainly attributable to SCC-derived IL-1α. Coculturing Fbs with SCC cells significantly augmented the matrigel invasive ability of SCC cells, which was downregulated when cocultured with CTSK knockdown Fbs or in the presence of neutralizing anti-IL-1α antibody. Conclusion: The CTSK-upregulated Fbs generated by SCC-derived IL-1α may play a crucial role in the progression and invasion of SCC. [ABSTRACT FROM AUTHOR]