Michał Rogowski-Tylman

An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes

Background:  Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC).

Risk factors in Central Poland for the development of superficial and nodular basal cell carcinomas

Introduction In the last decades the number of skin carcinomas has dramatically increased, which is mainly connected with changes in lifestyle, especially with common use of artificial light sources such as sunbeds. Basal cell carcinoma (BCC) is the most common form of skin cancer in white populations. Basal cell carcinomas are divided into subtypes, depending on their clinical picture and histology. The main groups are nodular (nBCC) and superficial (sBCC) ones. The major recognized risk factors for basal cell carcinoma (BCC) are exposure to chronic and intermittent burning doses of sunlight. Other risk factors leading to the development of the nBCC and sBCC subtypes of BCC are not well established. Material and methods An analysis of 123 patients with either nBCC or sBCC, living in Lodz, Poland, regarding various intrinsic and environmental parameters was undertaken following the histological diagnosis of BCC. Results No statistical differences were observed between the BCC subtype and sex, age, hair colour, eye colour, smoking, family history of skin cancer, occupation, or past episodes of sunburn. While sBCCs tended to occur on unexposed body sites in phototype I/II subjects who mainly avoided direct sunlight, nBCCs tended to occur on sun-exposed body sites in phototype III subjects who were frequently in direct sunlight. Conclusions Thus the development of particular BCC subtypes is partially dependent on phototype and personal sun behaviour.

Atopic dermatitis patients carrying G allele in -1082 G/A IL-10 polymorphism are predisposed to higher serum concentration of IL-10.

Introduction Atopic dermatitis (AD) is a chronic skin inflammatory disease in which Th2-derived cytokines play an essential role. Aim of the study was to assess interleukin 4, 10 and 13 (IL-4, IL-10 and IL-13) serum concentrations in AD patients and to correlate the values with the occurrence of genotypes of selected polymorphisms in genes encoding these cytokines. Material and methods Seventy-six AD patients (mean age 11.4 years) and 60 healthy controls were enrolled in the study. Blood samples were analyzed for IL-4, IL-10 and IL-13 concentrations with ELISA assay and genotyping for –590C/T IL-4, –1082A/G IL-10 and –1055C/T IL-13 polymorphisms with PCR-RFLP. Results The obtained results revealed statistically higher serum concentration of IL-10 and IL-13 in AD patients when compared to healthy controls (10.30 pg/ml vs. 8.51 pg/ml for IL-10 and 5.67 pg/ml vs. 4.98 pg/ml for IL-13). There were no significant differences between AD patients and controls in regard to IL-4 serum level (5.10 pg/ml vs. 7.1 pg/ml). Analyzing the association between level of the examined cytokines and genotype polymorphisms –590 C/T for the IL-4 gene, –1082 A/G for the IL-10 gene and –1055 C/T for the IL-13 gene, we found a statistically higher IL-10 serum level among carriers of the G allele in the –1082 G/A IL-10 polymorphism both in AD and control groups. We did not find any significant differences between serum level of IL-4 and IL-13 in regard to genotype occurrence in examined polymorphisms: –590 C/T for the IL-4 gene and –1055 C/T for the IL-13 gene. Conclusions The obtained results confirm the genetic background of IL-10 synthesis in the Polish population.

Suberythemal ultraviolet B radiation alters the expression of cell cycle‐related proteins in the epidermis of human subjects without leading to photoprotection

Background  Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis.

Sonic hedgehog pathway dysregulation in skin basal-cell carcinoma of a Polish population

Sonic hedgehog (Shh) pathway impairment plays a key role in the pathogenesis of basal-cell carcinomas (BCC), the most frequent skin tumor among Caucasians. Shh, Smo, and Gli2 family proteins are necessary for adequate and controlled cell proliferation. The aim of this study was to evaluate Shh, Smo, and Smo expression in BCC skin biopsies taken from sun-exposed areas. 41 BCC skin biopsies and 22 healthy skin specimens (the control group) taken from the same areas served as material for the study. All specimens were immunohistochemically stained with monoclonal antibodies directed against the chosen proteins. Shh and Smo expression (cytoplasmic pattern) were recorded semiquantitatively using a four-grade score (0-3). Gli2 expression (nuclear pattern) was determined using an image analysis system (semiautomatic function). The immunoexpression of the Shh and Smo proteins significantly increased in the BCC group, as compared with the normal controls (for Shh, the mean intensity was 1.67 in BCC vs. 1.17 in the control group, p < 0.001; for Smo, the mean intensity was 1.46 in BCC vs. 0.99 in the control group, p < 0.001). The staining for Gli2 in the BCC group was completely negative, but indicated the presence of Gli2 in the control patients (1.15 Gli2+ cells/100 cells). Sonic hedgehog pathway dysregulation may play an important role in skin cancerogenesis leading to BCC development.

Repeated suberythemal UVB preexposure protects against high-dose UVB-induced expression of vitamin D receptor protein in human Skin.

pression in acquired nevi is reminiscent of the heterogeneity of B-RAF mutations found in human nevi (Lin et al., 2009). It remains to be determined whether the mutant B-RAF is coexpressed with p16 or if activated B-RAF and loss of p16 contribute separately to the clonal expansion of melanocytes. Alternatively, activated B-RAF and p16 deficiency may co-exist in a small percentage of nevus cells to enhance melanocyte proliferation and drive neoplastic transformation. The absence of a mutant-specific B-RAF antibody has so far precluded the execution of such an analysis. It is well established that activated B-RAF can promote nevus formation in murine and fish melanoma models (Patton et al., 2005; Goel et al., 2009), and the arrested state of nevi does not appear to require p16 (Dhomen et al., 2009). Nevertheless, the influence of p16 loss on the development of B-RAF-induced nevi needs to be investigated in human melanocytic tumors. This is particularly relevant as p16 loss regulates the penetrance and latency of B-RAF-induced murine melanomas (Dhomen et al., 2009).

One week’s holiday sun exposure induces expression of photoaging biomarkers

INTRODUCTION Skin aging is accompanied by the upregulation of the expression of various matrix metalloproteinases (MMPs). It was shown that exposure to ultraviolet radiation (UVR) may induce skin expression of MMPs and dysregulation of the transforming growth factor beta (TGF-β)/Smad pathway. The aim of our study was to compare the effects of short holiday UVR exposure and lifetime UVR exposure, on the expression of MMP-8, TGF-β1, and Smad2 in human skin biopsies. MATERIAL AND METHODS Skin biopsies were taken from the outer upper arm of 15 elderly people with significant photoaging (mean age 64.1 years) (Group 1) and from 15 healthy young adult volunteers (mean age 24.1 y) who participated in a six-day sun holiday. Biopsies were taken twice: 24 hours before leaving for holiday (Group 2a) and 24 hours after returning (Group 2b). The expression of TGF-β1, Smad2, and MMP-8 was examined by immunochemistry and measured semiquantitatively by two independent pathologists. RESULTS The mean expression of TGF-β1 in dermal fibroblasts and keratinocytes in Group 1 and Group 2b was significantly lower than in Group 2a (0.54% ± 0.44% and 0.48% ± 0.51% vs. 1.48% ± 0.72%, respectively). The percentage of Smad2 (+) cells in Group 1 and Group 2b was lower than in Group 2a (2.13% ± 1.39% and 1.81% ± 1.16% vs. 4.13% ± 1.58%, respectively). The MMP-8 expression in Group 2b was 1.36% ± 0.68% and was significantly higher than in Group 1 (0.34% ± 0.42%) and Group 2a in which the protein was not detected (p < 0.001). CONCLUSIONS We conclude that the decrease in the expression of TGF-β1 and Smad2 is a persistent biomarker of skin photoaging, while the increased expression of MMP-8 in keratinocytes can be regarded as a marker of acute sun exposure.

Sunscreen applied at ≥ 2mg/cm2 during a sunny holiday prevents erythema; a biomarker of UVR-induced DNA damage and suppression of acquired immunity

Sun protection factor (SPF) is assessed with sunscreen applied at 2 mg cm−2. People typically apply around 0·8 mg cm−2 and use sunscreen daily for holidays. Such use results in erythema, which is a risk factor for skin cancer.

One week of exposure to sunlight induces progerin expression in human skin

1Department of Dermatology, Medical University of Lodz, Lodz, Poland 2Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, Lodz, Poland 3Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland 4Department of Pathology, Medical University of Lodz, Lodz, Poland 5St John’s Institute of Dermatology, King’s College London, London, UK Adv Dermatol Allergol 2017; XXXIV (6): 629–631 DOI: https://doi.org/10.5114/pdia.2016.62416

Can biologic treatment induce cutaneous focal mucinosis

Skin mucinosis is a rare skin disease which clinically manifests as firm papules and waxy nodules. We report a case of a 66-year-old female psoriatic patient who developed skin mucinosis during biological therapy. Because of a previous lack of response to the local and conventional systemic treatment of psoriasis, the patient received biological therapy (infliximab from June 2008 to May 2009 – initial clinical improvement and loss of treatment effectiveness in the 36th week of the therapy; adalimumab from June 2009 to January 2010 – lack effectiveness; ustekinumab from March 2012 to the present). Throughout 2 months we observed a manifestation of the skin mucinosis as well-demarcated, yellow and brown, papulo-nodular lesions of 5–10 mm in diameter, localized on the back. Histopathological examination with alcian blue staining demonstrated mucin deposits in the dermis. On the basis of clinical and histopathological findings, the diagnosis of cutaneous focal mucinosis was established. We present the case because of the extremely rare occurrence of the disease. Scarce literature and data suggest that there is an association between focal mucinosis and thyroid dysfunction, as well as possible adverse effects of biological therapy with TNF-α antagonists.