[Impaired expression of cell-cycle regulatory proteins in seborrheic keratosis]. / Narushenie ékspressii belkov-reguliatorov kletochnogo tsikla pri seboreinom keratoze.

Seborrheic keratosis (SK) is a benign skin tumor of unknown etiology and pathogenesis. Many details remain unclear despite that there have been a number of studies of cell-cycle abnormalities. AIM: to investigate the expression of the cell-cycle regulatory proteins p53 and p16 and the cell proliferation marker Ki-67 in SK. SUBJECTS AND METHODS: The investigation used intraoperative SK material obtained from 130 patients. Tumors were removed from UV-exposed parts of the body in 63 (48%) patients and from the places that were more often closed in 67 (51.5%). An immunohistochemical (IHC) study was performed using monoclonal antibodies to p53, p16, and Ki-67. RESULTS: A positive reaction with monoclonal antibodies to p53 was recorded in 66 (50.7%) SK samples. In 92.1% of cases, the expression of p53 was found in SK located at the sites that were most exposed to UV radiation (p=0.00001). A positive reaction with monoclonal antibodies to p16 was observed in all SK cases as cytoplasmic staining of more than 50% of the tumor cells: a strong staining in 63 SK samples (overexpression) and a weak staining in 67 SK ones. The level of p16 expression correlated with age (R=0.21; p=0.019) and SK location at the sites exposed to increased insolation (R=0.35; p=0.000038). Overexpressions of p53 and p16 were significantly more commonly recorded in irritated SK. The tumor proliferative activity by the level of Ki-67 expression was low (3.0 to 11.3%). The largest number (8.5±4.8%) of proliferating cells was recorded in irritated SK (p=0.0000001). CONCLUSION: The found disorders in the expression of cell-cycle regulatory proteins in SK are suggestive of tumor suppressor activation and keratinocyte senescence. There may be malignant tumor transformation in irritated SK in terms of the significant increase in the expression of p53, p16 in the presence of high cell proliferative activity.

[Role of IL-17A and neutrophilic granulocytes in the pathogenesis of psoriasis]. / Rol' IL-17A i neitrofil'nykh granulotsitov v patogeneze psoriaza.

OBJECTIVE: To study the expression of IL-17A in the inflammatory infiltrating cells in the plaques as one of the key points in the pathological process in moderate to severe psoriasis. MATERIAL AND METHODS: The material obtained from 50 patients with moderate and severe psoriasis was examined by an indirect immunofluorescence assay to determine the composition of cell infiltrate and the type of IL-17A-producing cells in the foci of lesion. The markers of lymphocytes (CD3), dendritic cells (CD11c), neutrophilic granulocytes (Mpo), and mast cells (Trp) were used. The proliferative activity of basal keratinocytes (Ki-67), the expression of IL-17A, and the co-expression of IL-17A, Mpo, and Trp were also studied. RESULTS: A positive correlation was established between the count of neutrophilic granulocytes in the infiltrate, the expression of IL-17A, and the number of neutrophils expressing IL-17A with the duration of the disease and the severity of the patient's condition. CONCLUSION: Neutrophilic granulocytes and their expression of IL-17A play one of the key roles in the pathogenesis of psoriasis.

[Trichilemmal carcinoma in a patient with squamous cell skin cancer]. / Trikholemmal'naia kartsinoma u patsienta s ploskokletochnym rakom kozhi.

Trichilemmal carcinoma is a rare skin tumor that mainly occurs in the elderly (mean age, 71 years) and is localized in the repeatedly sun-exposed areas, most commonly on the face, scalp, neck, and dorsa of the hands. Its differential diagnosis is made with squamous cell skin cancer, clear-cell porocarcinoma, hidradenocarcinoma, and melanoma. The prognosis of trichilemmal carcinoma is most favorable than that of other skin tumors during radical removal. The paper describes a case of an 80-year-old man with long-standing trichilemmal carcinoma of the skin in the area of the shoulder joint, which is concurrent with squamous cell cancer in another area of the skin.

[A case of solid pseudopapillary tumor of the pancreas: features of the course, difficulty in diagnosis]. / Nabliudenie solidno-psevdopapilliarnoi opukholi podzheludochnoi zhelezy: osobennosti techeniia, slozhnosti v diagnostike.

Solid pseudopapillary tumor is a low-grade malignant neoplasm of the pancreas. The clinical manifestations are variable, ranging from an asymptomatic course to cases with severe symptoms that dramatically impair the patients' status. The paper describes the rare case of a solid pseudopapillary tumor in a 34-year-old woman, which was accompanied by difficulties in the interpretation of clinical data and morphological patterns.

[Expression of epidermal growth factor receptor in patients with insulin resistance and seborrheic keratomas]. / Ékspressiia retseptora épidermal'nogo faktora rosta pri nalichii insulinorezistentnosti u patsientov s seboreinymi keratomami.

AIM: to study the expression of epidermal growth factor receptor (EGFR) in patients with seborrheic keratomas (SK) and insulin resistance (type 2 diabetes mellitus (DM2)) and in those without concomitant carbohydrate metabolic disturbances. SUBJECTS AND METHODS: 80 patients with SK were examined. According to the presence or absence of DM2, the patients were divided into 2 groups: 1) 40 patients with concomitant DM2; 2) 40 people without carbohydrate metabolic disturbances. DM2 was diagnosed on the basis of laboratory studies and an endocrinologist's consultation. Histological and immunohistochemical (IHC) examinations using anti-EGFR antibodies were performed; two intact skin sections from the patients with DM2 and two intact skin sections from those without carbohydrate metabolic disturbances were used as a control. RESULTS: The ICH examination using anti-EGFR monoclonal antibodies revealed that Group 1 showed intense diffuse membrane staining of more than 50% of the cells in 32 (80%) patients, moderate (30-50% cells) and weak (10-30% cells) staining in 6 (15%) and 2 (5%) patients, respectively. Marked EGFR expression was also noted in two intact skin biopsy specimens taken from patients with DM2. In Group 2, the staining intensity was weak in more than 10% but less than 30% of the SK cells in 28 (70%) patients; moderate EGFR expression was observed in 9 (22.5%) and diffuse, pronounced, staining in more than 50% of the SK cells was in 3 (7.5%) patients. The intact skin biopsy specimens taken from 2 patients without carbohydrate metabolic disturbances displayed a weak EGFR expression in the basal cell layer of the epidermis. CONCLUSION: EGFR overexpression in SK may be a result of metabolic disorders rather than a diagnostic sign of malignant neoplasms of the internal organs. The increased EGFR expression revealed in patients with SK and concomitant DM2 is caused by insulin resistance and hyperinsulinemia, in which the dysregulation of insulin signal transmission into the cell leads to changes in EGF synthesis and signaling pathway that regulates cell proliferation and growth.

[Current approaches to the morphologic diagnosis of different types of congenital epidermolysis bullosa]. / Sovremennye podkhody k morfologicheskoi diagnostike razlichnykh tipov vrozhdennogo bulleznogo epidermoliza.

Congenital epidermolysis bullosa (CEB) is an extensive group of hereditary skin diseases, the differential diagnosis of which is a challenge due to the rarity of this pathology and the diversity of its clinical manifestations. The determination of the type of CEB makes it possible to estimate its prognosis and to facilitate a prenatal diagnosis. AIM: to optimize the morphological diagnosis of different types of CEB. MATERIAL AND METHODS: 28 skin biopsies from 14 patients with different types of CEB were investigated. The investigators performed routine histological examination of skin fragments taken from a bullous area and immunofluorescence antigen mapping using the indirect immunofluorescence test (IIFT) with antibodies against structural proteins of the dermal-epidermal junction (laminin α3, ß3, and γ2 chains, keratins 5 and 14, types VII and XVII collagen, α6 and ß4 integrin subunits, desmoplakin, plectin, kindlin-1, and plakophillin) of the apparently unaffected skin. The intact skin of healthy individuals, which had been obtained during cosmetic operations, was used as controls in IIFT. RESULTS: Immunofluorescence antigen mapping could determine the type of CEB in all cases and in 86% of cases identify the protein, the impaired production of which was responsible for the development of the disease. CONCLUSION: Immunofluorescence antigen mapping is an integral part of the comprehensive morphological diagnosis of CEB, acting as an intermediate between the morphological verification of CEB diagnosis and the targeted search for mutations by a molecular genetic method.

[Role of the skin expression of neuropeptides, neurotrophins and their receptors in the pathogenesis of dermatoses].

OBJECTIVE: to define the role of neurotransmitters and their receptors in the development of itch and in the maintenance of a skin inflammatory response in patients with psoriasis and atopic dermatitis. MATERIAL AND METHODS: Skin biopsy specimens from 30 patients with psoriasis and 30 patients with atopic dermatitis were investigated by histological, immunoperoxidase, and indirect immunofluorescence assays. The investigators determined the expression of protein gene product 9.5 (PGP9.5), amphiregulin, semaphorin 3A, calcitonin gene-related peptide (CGRP) and its receptor (CGRP-R), nerve growth factor (NGF) and its receptor TrkA, and substance P (SP) and its receptor SP-R. The indirect immunofluorescence assay was used for quantitative analysis. The findings were statistically analyzed using a Statistica 10 program. RESULTS: Immunoperoxidase examination of the skin biopsy specimens from patients with atopic dermatitis and psoriasis revealed enhanced expression of amphiregulin, NGF, and PGP9.5, appearance of positively stained epidermal nerve fibers, and decreased expression of the nerve reduction factor semaphorin 3A in all cases. Some patients with atopic dermatitis and psoriasis showed increased expression of CGRP and CGRP-R, SP, SP-R, and TrkA. A pronounced inflammatory response was generally observed in these cases. CONCLUSION: The investigation performed suggests that atopic dermatitis and psoriasis are characterized by a larger number of epidermal nerve fibers and by a direct correlation between this indicator, disease severity, and itch intensity. The production of neuropeptides and neurotrophins is closely related to the development of a skin inflammatory response irrespective of its cause and dysregulation of these processes is likely to favor the body's sensitization and the chronic pattern the course of diseases.