Expression of Proton-Sensitive GPR31, GPR151, TASK1 and TASK3 in Common Skin Tumors

TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of TASK1, TASK3, GPR31 and GPR151 in squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), nevus cell nevi (NCN), and malignant melanomas (MMs). We performed immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express TASK1/3 and GPR31/151. The results show that BCCs are often negative for GPR31/151 as well as for TASK1/3, while nearly all SCCs express these markers. MMs and NCN show similar expression patterns. However, some tumors show a decreasing TASK1/3 expression in deeper dermal tumor tissue, while GPCRs were expressed more evenly. The lower frequency of GPR31/151 and TSAK1/3 expression in BCCs when compared to SCCs is a novel histological feature distinguishing these two entities. Moreover, BCCs also show lower expression of GPR31/151 and TASK1/3 as compared to NCN and MMs.

Sharing is Caring – A Systematic Review on how Frequently Dermoscopic Images are Shared in Inter-observer Investigations

Research interest in dermoscopy has accelerated, but the complete dermoscopic image sets used for inter-observer investigations for skin tumors are not often shared to the reader. The aim of this systematic review was to analyze what proportion of images depicting skin tumors are shared in the manuscripts of studies investigating inter-observer variation in the assessment of dermoscopic features and/or patterns. The Embase, MEDLINE, and Scopus databases were screened for eligible studies published from inception to July 2, 2020. For included investigations we extracted the proportion of lesion images presented in the manuscripts and or supplements. Overall, we included 61 studies (52 original investigations and 9 concise reports) in the time period of 1997 to 2020. These investigations combined, included 14,124 skin tumors of which 373 (3%) images were shared. Since data sharing must be promoted, this investigation should be a wake-up call for the dermatology research community and editorial offices.

Dermatoses in the hospital and their impact on quality of life

Sir, Dermatological pathologies may be responsible for the creation of a real handicap, affecting the patient’s self-esteem and their professional and social life. The aim of this study was to assess the impact of diseases on the quality of life of patients hospitalized at the dermatology department. The following was a retrospective study that included patients over eighteen years of age, hospitalized at the dermatology department of Hospital Mohammed VI in Oujda from January 2018 through December 2019. The Arabic version of the validated DLQI was used for all patients [1]. A total of 294 patients were collected, with a mean age of 53.95 years and a male-to-female ratio of 0.85. The most frequent reasons for hospitalization were infectious dermo-hypodermitis (n = 51), autoimmune bullous dermatosis (n = 23), severe drug eruption (n = 20), genodermatosis (n = 17), melanocytic (n = 9) and non-melanocytic skin tumors (n = 17), severe psoriasis (n = 17), cutaneous lymphoma (n = 11), alopecia areata (n = 10), dermatomyositis (n = 8), and Verneuil’s disease (n = 5). The DLQI was impossible to calculate in eleven patients. The mean DLQI in all patients was 10.20, corresponding to a moderate effect on quality of life. The mean DLQI was as follows: Verneuil’s disease at 17.4, severe psoriasis at 16.6, dermatomyositis at 14.42, genodermatosis at 12.37, cutaneous lymphoma at 11.45, severe drug eruption at 11, alopecia areata at 10.5, AIBD at 9.67, skin tumors at 7.76, and infectious dermo-hypodermitis at 7.52. The DLQI was the first index measuring quality of life in dermatology and is still widely used today[2]. The number of publications concerning the impact of dermatological pathologies on quality of life has increased in recent years [3]. Our results showed that the DLQI was higher in patients with Verneuil’s disease, severe psoriasis, and dermatomyositis. These results agree with the data of the literature, many publications have shown that psoriasis seriously impaired the quality of life and was responsible of social anxiety in patients [4]. Verneuil’s disease is also responsible of a significant impairment on quality of life mainly due to the sexual disorders caused by this pathology [5]. Another study on dermatomyositis showed that there is a significant correlation between the severity of skin signs and the quality of life of patients [6]. Dermatological pathologies are distinguished from other pathologies by their displaying character, which is responsible for a significant impact on the patient’s quality of life. The management of dermatology patients requires psychological support in addition to conventional therapy. However, these pathologies are still not recognized as long-term illnesses in Morocco.

K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors

NKIRAS1 and NKIRAS2 (also called as κB-Ras) were identified as members of the atypical RAS family that suppress the transcription factor NF-κB. However, their function in carcinogenesis is still controversial. To clarify how NKIRAS acts on cellular transformation, we generated transgenic mice in which NKIRAS2 was forcibly expressed using a cytokeratin 15 (K15) promoter, which is mainly activated in follicle bulge cells. The ectopic expression of NKIRAS2 was mainly detected in follicle bulges of transgenic mice with NKIRAS2 but not in wild type mice. K15 promoter-driven expression of NKIRAS2 failed to affect the development of epidermis, which was evaluated using the expression of K10, K14, K15 and filaggrin. However, K15 promoter-driven expression of NKIRAS2 effectively suppressed the development of skin tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA). This observation suggested that NKIRAS seemed to function as a tumor suppressor in follicle bulges. However, in the case of oncogenic HRAS-driven cellular transformation of murine fibroblasts, knockdown of NKIRAS2 expression drastically suppressed HRAS-mutant-provoked cellular transformation, suggesting that NKIRAS2 was required for the cellular transformation of murine fibroblasts. Furthermore, moderate enforced expression of NKIRAS2 augmented oncogenic HRAS-provoked cellular transformation, whereas an excess NKIRAS2 expression converted its functional role into a tumor suppressive phenotype, suggesting that NKIRAS seemed to exhibit a biphasic bell-shaped enhancing effect on HRAS-mutant-provoked oncogenic activity. Taken together, the functional role of NKIRAS in carcinogenesis is most likely determined by not only cellular context but also its expression level.

Molecular Profile of Skin Cancer

Neoplasia occurs as a result of genetic mutations. Research evaluating the association between gene mutations and skin cancer is limited and has produced inconsistent results. There are no established guidelines for screening skin cancer at molecular level. It should also be noted that the combinations of some mutations may play a role in skin tumors’ biology and immune response. There are three major types of skin cancer, and the originality of this study comes from its approach of each of them.

Skin Tumors among Biopsy Samples in Patients Attending Dermatological Out Patient Department in a Tertiary Care Hospital of Nepal: A Descriptive Cross-sectional Study

Introduction: Skin tumors are on the rise in the Nepalese community. The different morphological pattern of skin tumors requires its meticulous categorization for understanding its effect on prognosis and treatment. Our study aimed at studying the prevalence of skin tumors among the skin biopsies performed in the dermatology outpatient department in a tertiary care hospital of Nepal. Methods: A descriptive cross-sectional study was done from skin biopsy samples from 1st January, 2017 to 31st December, 2019, at a tertiary care center. Ethical clearance was taken from the institutional review committee (IRC), Ref No: 056-077/078. Convenience sampling was done. A self-designed proforma containing questions on the patients' socio-demographic data and clinical details were used, and a biopsy of those clinically suspected to have skin tumors was done. Skin tumors were classified according to the World Health Organization 2018 classification of skin tumors. Data were analyzed using Statistical Package for the Social Sciences Version 16. Point estimate at 95% Confidence Interval was done, and frequency and proportion were calculated. Results: A total of 671 skin biopsies were done during this study, out of which 125 (18.63%) at 95% Confidence Interval (15.68-21.57) were diagnosed with skin tumors. Among them, 77 (61.6%) were female, and 48 (38.4%) were male. Among the diagnosed cases, 105 (84%) were benign, and 20 (16%) were malignant. Conclusions: The findings from our study show the increasing prevalence of skin tumors, and the results were comparable to other similar studies conducted in various parts of Nepal.

Cutaneous reaction to sea urchin spines

A 35-year-old male returned from vacation in Hawaii where he went scuba diving and snorkeling. While snorkeling, he stepped on a sea urchin and sustained injuries to the dorsal aspect of his right foot. He began to swim back to shore when he felt significant pain and began removing visible spines when he reached shore. He saw a physician in Hawaii who removed remaining spines and started a treatment regimen of cephalexin 500 mg QID. Patient followed up 2 weeks later with his home dermatologist for persistent granuloma and was given 15-day course of oral doxycycline 50 mg BID with near full recovery within 2 weeks. Even physicians practicing inland need to be aware of coastal injuries and reactions as they can mimic other common skin tumors such as keratoacanthomas.