A Study of FoxO1, mTOR, miR-21, miR-29b, and miR-98 Expression Levels Regarding Metabolic Syndrome in Acne Vulgaris Patients.

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disease caused by the mechanistic target of rapamycin complex 1 (mTORC1). forkhead box protein (Fox) O1 is known to regulate the relationship between the mTORC1 signaling pathway and insulin resistance (IR). Increased mTORC1 signaling is known to predispose one to diseases such as insulin resistance (IR), obesity, and diabetes mellitus. One of the major components of mTORC1 is mTOR. FoxO1 and mTOR play key roles in the onset and progression of metabolic syndrome (MetS). In this study, we aimed to elucidate the relationship between AV and MetS through FoxO1 and mTOR signaling pathways and microRNAs (miRs) associated with these signaling pathways. METHODS: We examined 20 AV patients without MetS, 16 AV patients with MetS, and 20 healthy controls. The demographic characteristics of the patients, MetS parameters, clinical severity of AV (Global Acne Grading System, GAGS), and the homeostasis model assessment (HOMA) values were compared between the groups. In addition, the expression levels of FoxO1 and mTOR genes, along with the expression levels of miR-21, miR-29b, and miR-98, were assessed in skin biopsy samples from all groups using real-time polymerase chain reaction methods. FoxO1, mTOR, and miRNA expression levels were recorded as fold change. RESULTS: The mean age of patients with AV without MetS was statistically lower. In AV patients with MetS, those with moderate GAGS scores had statistically significantly higher HOMA values than those with mild GAGS scores. FoxO1 expression was significantly lower in AV patients compared to controls. The mTOR expression levels of AV patients with MetS were significantly higher than the other two groups. The expression levels of miR-21 and miR-29b were significantly increased in the group of AV patients with MetS compared to the group of AV patients without MetS. CONCLUSIONS: These results suggested that the mTOR pathway may play an important role in explaining the relationship between AV and MetS in acne pathogenesis. They also suggested that miR-21 and miR-29b play a role in the inflammatory process of AV.

Methylation status, mRNA and protein expression of the SMAD4 gene in patients with non-melanocytic skin cancers.

BACKGROUND: SMAD4 is a potent tumor suppressor. SMAD4 loss increases genomic instability and plays a critical role in the DNA damage response that leads to skin cancer development. We aimed to investigate SMAD4 methylation effects on mRNA and protein expression of SMAD4 in cancer and healthy tissues from patients with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and basosquamous skin cancer (BSC). METHODS AND RESULTS: The study included 17 BCC, 24 cSCC and nine BSC patients. DNA and RNA were isolated from cancerous and healthy tissues following punch biopsy. Methylation-specific polymerase chain reaction (PCR) and real-time quantitative PCR methods were used to examine SMAD4 promoter methylation and SMAD4 mRNA levels, respectively. The percentage and intensity of staining of the SMAD4 protein were determined by immunohistochemistry. The percentage of SMAD4 methylation was increased in the patients with BCC (p = 0.007), cSCC (p = 0.004), and BSC (p = 0.018) compared to the healthy tissue. SMAD4 mRNA expression was decreased in the patients with BCC (p˂0.001), cSCC (p˂0.001), and BSC (p = 0.008). The staining characteristic of SMAD4 protein was negative in the cancer tissues of the patients with cSCC (p = 0.00). Lower SMAD4 mRNA levels were observed in the poorly differentiated cSCC patients (p = 0.001). The staining characteristics of the SMAD4 protein were related to age and chronic sun exposure. CONCLUSIONS: Hypermethylation of SMAD4 and reduced SMAD4 mRNA expression were found to play a role in the pathogenesis of BCC, cSCC, and BSC. A decrease in SMAD4 protein expression level was observed only in cSCC patients. This suggests that epigenetic alterations to the SMAD4 gene are associated with cSCC. TRIAL REGISTRATION: The name of the trial register: SMAD4 Methylation and Expression Levels in Non-melanocytic Skin Cancers; SMAD4 Protein Positivity. The registration number: NCT04759261 ( https://clinicaltrials.gov/ct2/results?term=NCT04759261 ).

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas.

BACKGROUND: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). OBJECTIVES: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. METHODS: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. RESULTS: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p=0.004), tumor size (p=0.023), tumor location in the H zone of the face (p=0.005), and aggressive histopathological subtype (p=0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. STUDY LIMITATIONS: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. CONCLUSIONS: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Clinical, Dermoscopic and Histopathological Evaluation of Basal Cell Carcinoma.

INTRODUCTION: Dermoscopy aids in identifying histopathological subtypes and the presence of clinically undetectable pigmentation in basal cell carcinoma (BCC). OBJECTIVES: To investigate the dermoscopic features of BCC subtypes and better understand non-classical dermoscopic patterns. METHODS: Clinical and histopathological findings were recorded by a dermatologist who was blinded to the dermoscopic images. Dermoscopic images were interpreted by two independent dermatologists blinded to the patients' clinical and histopathologic diagnosis. Agreement between the two evaluators and with histopathological findings was evaluated using Cohen's kappa coefficient analysis. RESULTS: The study included a total of 96 BBC patients with 6 histopathologic variants: nodular (n=48, 50%), infiltrative (n=14, 14.6%), mixed (n=11, 11.5%), superficial (n=10, 10.4%), basosquamous (n=10, 10.4%), and micronodular (n=3, 3.1%). Clinical and dermoscopic diagnosis of pigmented BCC showed high agreement with histopathological diagnosis. The most common dermoscopic findings according to subtype were as follows: nodular BCC: shiny white-red structureless background (85.4%), white structureless areas (75%), and arborizing vessels (70.7%); infiltrative BCC: shiny white-red structureless background (92.9%), white structureless areas (78.6%), arborizing vessels (71.4%); mixed BCC: shiny white-red structureless background (72.7%), white structureless areas (54.4%), and short fine telangiectasias (54.4%); superficial BCC: shiny white-red structureless background (100%), short fine telangiectasias (70%); basosquamous BCC: shiny white-red structureless background (100%), white structureless areas (80%), keratin masses (80%); micronodular BCC: short fine telangiectasias (100%). CONCLUSIONS: In this study, arborizing vessels were the most common classical dermoscopic feature of BCC, while shiny white-red structureless background and white structureless areas were the most frequent non-classical dermoscopic features.

A multicentre prospective analysis of the incidence of pemphigoid diseases in Turkey.

BACKGROUND: The differentiation between the pemphigoid diseases is essential for treatment and prognosis. In Turkey, data on the incidence of these diseases are insufficient. Our aim in this study is to determine the incidence, demographics and clinical characteristics associated with diseases of the pemphigoid group. METHODS: We prospectively analysed 295 patients with pemphigoid who visited dermatology clinics of tertiary referral hospitals in 12 different regions of Turkey within a year. The diagnosis was based on clinical, histopathological, direct immunofluorescence (DIF) and serological (multivariant enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence and mosaic-based BIOCHIP) examinations. Clinical and demographic findings, aetiological factors and concomitant diseases observed in the patients were recorded. RESULTS: A total of 295 (female/male ratio: 1.7/1) patients with pemphigoid were diagnosed in 1-year period. The overall incidence rate of pemphigoid diseases was found to be 3.55 cases per million-years. The ratio of pemphigoid group diseases to pemphigus group diseases was 1.6. The most common pemphigoid type was bullous pemphigoid (BP, 93.2%). The others were epidermolysis bullosa acquisita (3.1%), pemphigoid gestationis (2.4%), linear IgA disease (1%) and mucous membrane pemphigoid (0.3%). The most common (26.8%) possible trigger of the bullous pemphigoid was gliptin derivative drugs. The most common concomitant diseases with pemphigoid were cardiovascular (27.8%) and neurological diseases (23.7%). CONCLUSIONS: This study showed that the increased frequency of bullous pemphigoid reversed the pemphigoid/pemphigus ratio in Turkey. Further studies are warranted regarding the reasons for this increase.

A case of extragenital linear lichen sclerosus along the lines of Blaschko responding to methotrexate.

Lichen sclerosus, a rare, chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin, is usually asymptomatic and affects both sexes. The exact cause of lichen sclerosus is unknown. Extragenital lichen sclerosus may be localized or disseminated. Linear extragenital lichen sclerosus following the lines of Blaschko is an exceptionally rare form. A 66-year-old female patient presented with a sclerotic plaque extending from the dorsum of the right hand toward the elbow. The lesion first appeared on the right hand but spread toward the elbow within 1 year. The histological findings were consistent with a diagnosis of lichen sclerosus. We therefore diagnosed extragenital linear lichen sclerosus and achieved a good response with methotrexate.