Features of skinfold thickness in men with benign nevi

Nevi, although benign neoplasms of the skin, but have a certain tendency to malignancy, which is influenced by various external and internal human factors. Predicting the risk of benign nevi against this background is an important topic for experimental research. The aim of the study was to establish the features of the skinfold thickness (SFT) in men of the first adult age with benign nevi. SFT was determined according to the Bunak scheme for men (aged 22-35 years) with melanocyte benign simple nevi (n=34), melanocyte benign dysplastic nevi (n=27), melanocyte benign congenital nevi (n=14) and non-melanocyte benign (n=17). The control group – SFT of 82 practically healthy men of the same age group was selected from the data bank of the Research Center of National Pirogov Memorial Medical University, Vinnytsya. Statistical processing of the results was performed in the license package “Statistica 5.5” using non-parametric evaluation methods. It was found that in practically healthy men higher than in patients – SFT on the anterior and posterior surfaces of the shoulder and thigh (in all groups of patients); SFT on the forearm, at the lower angle of the scapula, chest and shin (only in patients with melanocyte benign dysplastic nevi). Also in healthy men are found lower than in patients – SFT on the side (in all groups of patients); SFT in the abdomen (in patients with melanocyte benign simple and non-melanocyte benign nevi). When comparing SFT between patients with benign nevi, in most cases, lower values of SFT found in patients with melanocyte benign dysplastic nevi. The obtained results indicate the initial manifestations of abdominal (android) type of fat deposition in the body in patients with benign nevi (most pronounced in patients with melanocyte benign simple nevi).

Features of total and longitudinal body sizes in men with benign nevi

The use of anthropometric markers to predict the onset or severity of the disease is key to solving the problem of preventive medicine and can be an indispensable tool in preventive examinations in schools, universities and industries. The purpose of the study was to establish total and longitudinal body sizes in men of the first mature age with benign nevi. Anthropometry (determination of total and longitudinal body sizes) was performed according to Bunak’s scheme for men (aged 22-35 years) patients with melanocytic benign simple nevi (n=34), melanocytic benign dysplastic nevi (n=27), melanocytic benign congenital nevi (n=14) and non-melanocytic benign nevi (n=17). As a control from the data bank of the research center of National Pirogov Memorial Medical University, Vinnytsya selected total and longitudinal body sizes of 82 practically healthy men of the same age group. Statistical processing of the obtained results was performed in the license package “Statistica 5.5” using non-parametric evaluation methods. It was found that the mass and surface area of the body in healthy men is lower than in patients (except for dysplastic nevi), and in patients with dysplastic nevi – lower than in patients with non-melanocytic nevi; the height of the suprathoracic, acromial and finger anthropometric points in healthy men is lower than in patients with nevi (except for the acromial point height in patients with dysplastic nevi), and the height of the pubic and acetabular anthropometric points – in healthy men is greater than in patients with simple (only pubic point) and dysplastic nevi; in addition, the height of the pubic and acetabular anthropometric points in patients with simple nevi is lower than in patients with non-melanocytic nevi and congenital nevi (only for the acetabulum height). Given the height of anthropometric points and the fact that body length between healthy and sick men has no significant or tendency differences, in sick men we observe a longer torso and shorter lower extremities (most pronounced in patients with simple and dysplastic nevi), which is a manifestation of “subpathological” constitutional types, which indicate a longer torso and shorter lower extremities.

ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1

Autophagy is a highly conserved cellular process in which intracellular proteins and organelles are sequestered and degraded after the fusion of double-membrane vesicles known as autophagosomes with lysosomes. The process of autophagy is dependent on autophagy-related (ATG) proteins. The role of autophagy in cancer is very complex and still elusive. We investigated the expression of ATG proteins in benign nevi, primary and metastatic melanoma tissues using customized tissue microarrays (TMA). Results from immunohistochemistry show that the expression of ATG5 and ATG7 is significantly reduced in melanoma tissues compared to benign nevi. This reduction correlated with changes in the expression of autophagic activity markers, suggesting decreased basal levels of autophagy in primary and metastatic melanomas. Furthermore, the analysis of survival data of melanoma patients revealed an association between reduced ATG5 and ATG7 levels with an unfavourable clinical outcome. Currently, the mechanisms regulating ATG expression levels in human melanoma remains unknown. Using bioinformatic predictions of transcription factor (TF) binding motifs in accessible chromatin of primary melanocytes, we identified new TFs involved in the regulation of core ATGs. We then show that nuclear respiratory factor 1 (NRF1) stimulates the production of mRNA and protein as well as the promoter activity of ATG5 and ATG7. Moreover, NRF1 deficiency increased in vitro migration of melanoma cells. Our results support the concept that reduced autophagic activity contributes to melanoma development and progression, and identifies NRF1 as a novel TF involved in the regulation of both ATG5 and ATG7 genes.

OCT-Angiography in Early Choroidal Melanoma and Choroidal Nevi

Purpose: To study the features of small choroidal melanoma and choroidal nevi angioarchitectonics using the optical coherence tomography angiography (OCTA).Patients and methods. We examined 128 patients with small choroidal neoplasms: 41 — with small choroidal melanoma (group 1), 42 — with suspicious nevi (group 2) and 45 — with benign nevi (group 3). All patients underwent general ophthalmic examinations and special instrumental diagnostic methods (ultrasound examination (US), fluorescence angiography (FA), spectral optical coherence tomography (SOCT), OCTA).Results. OCTA in all patients with small choroidal melanoma showed neovascular network under retinal pigment epithelium. We found a looped, cranked-twisted, heterogeneous vascular network with uneven clearance and with numerous bends and weaves, located under the vessels of retina. The limiting avascular zone corresponding to the tumor slope was determined in 19 (46.3 %) of 41 cases. There was a rim of dilated hyperreflective choriocapillaries on the periphery of the tumor. We identified hyperreflective homogeneous enlarged choriocapillaries in the focus area with a brighter glow than the surrounding choriocapillaries in 39 (92.9 %) of 42 patients with suspicious choroidal nevus. We detected an avascular zone with surrounding extended hyperreflective choriocapillaries in the center of the nevus in 3 (7.1 %) of 42 cases. We diagnosed homogeneous isoreflective choriocapillaries similar in brightness to the surrounding vessels in all 45 patients with benign nevi.Conclusions. Thus, the complex of clinical and instrumental methods, including OCTA, makes it possible to establish the diagnosis of malignant tumor of the choroid in early stages. At the same time, OCTA: 1) allows to visualize of the tumor vessels in the choroidal layer in 100 % of cases of in small choroidal melanoma; 2) makes it possible to distinguish the newly formed tumor vessels from the choriocapillaries in case of small choroidal melanoma; 3) provides an opportunity to establish the correct diagnosis and provide timely assistance to patients with benign and malignant choroidal tumors.

A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence

The senescence response to oncogenes is believed to be a barrier to oncogenic transformation in premalignant lesions, and describing the mechanisms by which tumor cells evade this response is important for early diagnosis and treatment. The male germ cell-associated protein SSX2 is ectopically expressed in many types of cancer and is functionally involved in regulating chromatin structure and supporting cell proliferation. Similar to many well-characterized oncogenes, SSX2 has the ability to induce senescence in cells. In this study, we performed a functional genetic screen to identify proteins implicated in SSX2-induced senescence and identified several subunits of the Mediator complex, which is central in regulating RNA polymerase-mediated transcription. Further experiments showed that reduced levels of MED1, MED4, and MED14 perturbed the development of senescence in SSX2-expressing cells. In contrast, knockdown of MED1 did not prevent development of B-Raf- and Epirubicin-induced senescence, suggesting that Mediator may be specifically linked to the cellular functions of SSX2 that may lead to development of senescence or be central in a SSX2-specific senescence response. Indeed, immunostaining of melanoma tumors, which often express SSX proteins, exhibited altered levels of MED1 compared to benign nevi. Similarly, RNA-seq analysis suggested that MED1, MED4, and MED14 were downregulated in some tumors, while upregulated in others. In conclusion, our study reveals the Mediator complex as essential for SSX2-induced senescence and suggests that changes in Mediator activity could be instrumental for tumorigenesis.

Keratinocyte desmoglein 1 regulates the epidermal microenvironment and tanning response

ABSTRACTCoordinated responses to environmental stimuli within the keratinocyte:melanocyte niche are poorly understood. Desmoglein 1 (Dsg1), a keratinocyte-specific desmosomal cell-cell adhesion protein with emerging signaling roles, is reduced by ultraviolet light radiation. Loss-of-function Dsg1 mutations elevate keratinocyte cytokines in Severe dermatitis, multiple Allergies, and Metabolic wasting (SAM) syndrome. We asked whether Dsg1 regulates keratinocyte:melanocyte paracrine communication to induce the tanning response. Dsg1-silenced keratinocytes increasedPro-opiomelanocortinmRNA and cytokine secretion. Melanocytes treated with conditioned media from Dsg1-silenced keratinocytes exhibited increasedMitfandTrp1mRNA, melanin secretion, and dendrite length. Inhibiting the melanocyte pigment-associated melanocortin 1 receptor reduced pigment secretion in response to Dsg1-deficient conditioned media. Melanocytes incorporated into Dsg1-deficient human skin equivalents relocalized suprabasally, reminiscent of early melanoma pagetoid behavior. Dsg1 decreased in keratinocytes surrounding dysplastic nevi and early melanoma, but not benign nevi. We posit Dsg1 controls keratinocyte:melanocyte communication through paracrine signaling, which goes awry upon Dsg1 loss in melanoma development.

DERMOSCOPY OF THE MONTH Nevi with Site-Related Atypia

The term “nevi of special sites” refers to melanocytic nevi of specific anatomic locations including the breast, axillae, umbilicus, genitalia, flexural areas, acral surfaces, ear, scalp and the conjunctiva. Nevi from these anatomic sites display sometimes dermoscopic and histological features of melanoma, resulting in unnecessarily high rates of excisions and re-excisions. Some authors have categorized nevi excised in the axillary, breast, umbilical and perineal areas as the nevi of the milk line. Two patients, a 32-year-old female and 23-year-old male with breast and periumbilical pigmented lesions, presented to our Department during 2017. Dermoscopy revealed features that were highly specific for melanoma. Excisional biopsies were done and histopathology revealed benign nevi with present site-related atypia. Irregular blotches, non-uniform radial streaks, blue-gray veil, and regression are the most specific features of melanoma of the breast and flexural areas. Excision is always recommended in pigmented lesions on the breast and flexural areas, which exhibit these features. However, larger studies are needed to define specific criteria required to distinguish special-site nevi from melanoma.