Automated Assessment of the Area of Infiltration by CD8+ Cells in Gastric Carcinoma and Areas of Normal Mucosa as a Significant Prognostic Factor.

In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8+ cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8+ cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression).

Cell Sheets of Mesenchymal Stromal Cells Effectively Stimulate Healing of Deep Soft Tissue Defects.

We used rat model of splinted defect of the skin and soft tissues to compare the efficiency f mesenchymal stromal cells applied in sheets or in suspension for the treatment of these injuries. Transplantation of mesenchymal stromal cells significantly accelerated wound healing in comparison with the control. In the group treated by application of mesenchymal stromal cell sheets, the defect was closed by day 28, in the group treated with cell suspension by day 35, and in the control group after 49 days. According to histological analysis of the tissue samples, the formation of the granulation tissue and fibrosis occurred earlier after application of mesenchymal stromal cells. Application of mesenchymal stromal cells in the form of cell sheets demonstrated high efficiency, which allowed us to consider this approach as a promising method of healing of skin and soft tissue injuries.

Experimental Evaluation of the Properties of 3D Porous Bone Substitute Based on Calcium Phosphate on the Model of Monocortical Diaphysial Femur Defect in Rats.

A new alloplastic high-permeable material based on tricalcium phosphate with Kelvin architectonics created by stereolithographic 3D-printing was studied in vivo. A monocortical defect of the femur was modeled in rats and the material was implanted into the defect area. In 24 weeks, the animals were euthanized and histological examination of the defect area was performed. One femur fracture with fixator migration was recorded after implantation of the studied material and the reference chronOS synthetic material. The studied material demonstrated better osteoconductive properties then traditional osteoplastic material, which was seen from greater number of bone trabeculae and their area in the defect area.

[The expression of claudins in colonic neoplasms]. / Osobennosti ekspressii klaudinov v novoobrazovaniyakh tolstoi kishki.

AIM: the evaluation of localization claudin-1, -3 and -4 types of cancer and colon polyps. MATERIAL AND METHODS: The study included 32 colon adenocarcinoma and 86 polyps. Antibody claudin-1; -3 and -4 were used as immunohistochemical markers in this study. RESULTS: 84/118, 64/118, 52/118 reaction with claudin-1, claudin-3 and claudin-4 in cancer and colon polyps had a membrane localization, respectively. In 33 (27.9%) cases was found paradoxical reaction claudin-1; in 50 (42.4%) - a paradoxical reaction claudin-3 in 66 (55.9%) - a paradoxical reaction claudin-4. Among the paradoxical claudin reaction nuclear localization of marker was observed relatively rarely: claudin-3 in 2.5% cases of colon cancer; claudin-4 in 8.5% of colon polyps. CONCLUSION: Mislocalization claudin-3 to nucleus in colon cancer and mislocalization claudin-4 to nucleus in adenomas of the colon were detected for the first time. The potential reasons for the paradoxical expression are discussed and a review of the literature, related all the alleged mechanisms of this mislocalization is provided.

[Unified requirements for the structure of the diagnosis to improving national morbidity ststistics and causes of death].

The overall structure of the diagnosis should be presented underlying disease; complications of underlying disease and coexistent disease. If patient has other significant conditions contributing to the death (comorbidity), they should be included in the diagnosis after underlying disease as concurrent disease, polypathia or background diseases (condition). The category «underlying disease¼ should include only the disease (condition), which by itself or through the complications can lead to death and should be recorded in Part I of the medical certificate of cause of death. Other significant conditions contributing to the death (comorbidity) and defined as concurrent disease, polypathia or background diseases (condition), should be recorded in Part II of the medical certificate of cause of death. Coexistent diseases shall not be taken into account of the statistics of causes of death, and therefore they should not stand in a medical certificate of cause of death.

[New approaches to the classification, grading, and prognosis of renal cell carcinoma].

Renal cell carcinoma is a heterogeneous group of tumors. Frequent revisions of its histological classification and TNM staging system complicate the retrospective studies of large patient groups and hamper the estimation of survival rates and quality of life for patients. Due to improving therapeutic possibilities, the problems of the staging, morphological diagnosis, grading, and determination of prognostic factors of renal cell carcinomas have assumed a particular significance. Despite the long-term history of studies dealing with renal cell carcinoma, there is no general agreement among specialists at to these issues. The paper reviews the recent International Society of Urological Pathology Consensus held in Vancouver in March 2013.

[Procedure for coding the causes of death in some circulatory system diseases].

The paper deals with the unification of requirements for coding the causes of death in circulatory system diseases, by taking into account the recently updated ICD-10 and the Consensus of the Expert Council Task Force on Pathological Anatomy, Ministry of Health of the Russian Federation (27 February 2014).

[Effect of coenzyme Q10 on rat myocardiumin the acute stage of experimental infarction].

The influence of coenzyme Q10 (CoQ10) on early ischemic deterioration was studied on Wistar rats with experimental myocardial infarction. CoQ10 (30 mg/kg) was injected intravenously 10 min after coronary artery occlusion, and morphometric analysis was performed for 72 h after the onset of ischemia. CoQ10-treated rats had restricted total myocardial damage (by 52%), including areas of necrosis (by 84%) and areas of cellular inflammatory infiltration (by 38%) as compared to saline-treated rats (p < 0.001).

[The alternative way of colorectal cancer developing. The histogenetic and molecular features of serrated lesions (review, continued)].

The occurrence of colorectal cancer can be traced in two ways: from conventional adenomas with the APC-gene mutation (model Fearon-Vogelstein) and the "serrated way", that has a unique genetic profile and morphological characteristics at the early stages. These neoplasms are determined from 7 to 9%. The risk of developing cancer of them is 7.5-15%. Precursors of epithelial neoplasia are aberrant crypts foci. About 20% of colorectal cancer demonstrated the common defects in DNA methylation (CIMP-positive profile), mutations BRAF (KRAS)--oncogenes, microsatellite instability (MSI). The serrated lesions may have these mutations. Serrated polyposis syndrome has specific genetic changes associated with biallelic mutation MUTYH also. Risk of colorectal cancer is very high in this syndrome and is more than 50%. Often the synchronous or metachronous cancers presence. They are usually accompanied by MSI-H and represented serrated morphology too. Understanding epigenetic ways and molecular features of serrated lesions gives an knowledge of their clinical significance and provides the evidence for the treatment and monitoring of patients with this disease. This review is devoted to these issues.

[Prognostic value of the expression of adhesion molecules for non-clear-cell variants of renal cell carcinoma].

The prognostic value of the expression of the adhesion molecules CD44, EMA, and E-cadherin was studied using surgical specimens of 105 renal cell carcinomas (54 papillary, 39 chromophobic, and 12 clear-cell ones). Stages 3-4 tumors showed hyperexpression of all the above proteins (the distribution was estimated by chi2 and Fisher's exact tests). Furthermore, CD44 was found to be an independent unfavorable factor to predict renal cell carcinoma: with its hyperexpression, the 5-year estimated survival rate decreased by 52% (Kaplan-Meier method; p = 0.018). The expression of EMA and E-cadherin was significantly associated with the stage and, to some extent, grade of tumor differentiation; however, it is necessary to study more observations to define the prognostic role of these proteins.

Detection, Role and Prognostic Value of Cancer-associated Fibroblasts in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) - mesenchymal cells in the tumor stroma, play one of the leading roles in tumor progression in many different tumors, including colorectal cancer. Scientists have described many markers for CAFs, but none of them is specific. We performed immunohistochemistry tests using five antibodies (αSMA, POD, FAP, PDGFRα, PDGFRß) to investigate CAFs in three zones of 49 colorectal adenocarcinomas: apical, central, and invasive edge. We revealed the reliable correlation between high PDGFRß and PDGFRα value in the apical zone and deeper invasion (T3-T4) (p = 0.0281 and p = 0.0137). High αSMA level in apical zone (p = 0.0001), αSMA level in central zone (p = 0.019), POD level in apical zone (p = 0.0222), POD level in central zone (p = 0.0206) and PDGFRß level in apical zone (p = 0.014) correlated reliably with the presence of metastasis in lymphatic nodules. For the first time, focused on the inner layer of CAF adjacent to tumor complexes. We observed that cases with inner αSMA expression were significantly more often (p = 0.023) characterized by the presence of regional lymph node metastasis compared with cases with mix of CAF markers (p = 0.007) and with cases with inner POD expression (p = 0.024). The found relationships between the level of markers and the presence of metastases indicate their clinical significance.

[Markers of stromal invasion during background and precancerous changes of the glandular epithelium and in adenocarcinoma of the cervix uteri].

UNLABELLED: It is very difficult to identify stromal invasion when the glandular epithelium of the cervix uteri is involved. It is necessary to draw a clear distinction between its glandular structures and adenocarcinoma in situ, involving the preexisting crypts and invasive glands. An attempt was made to assess the possibilities of using as markers of invasion the following stromal proteins and adhesion molecules: CD44, E-cadherin, beta-catenin, tenascin, and laminin. METHODS: Fifty-three cases of benign glandular changes, 66 cases of dysplasias and adenocarcinomas in situ, and 47 cases of invasive adenocarcinoma were examined. An immunohistochemical study was performed according to the standard protocol using the antibodies to CD44, laminin, tenascin, E-cadherin, and beta-catenin and a semiquantitative assessment of results was made. RESULTS: CD44 was found to be redistributed from the cells to the tumor stroma. CD44 was not detected in the stroma surrounding the intact glands, so were benign epithelial changes. In the tumor environment, there was, on the contrary, a reaction with CD44 in 74.5% of invasive adenocarcinomas cases (p < 0.05). The expression of tenascin in the invasive adenocarcinomas and around the foci of early stromal invasion significantly exceeded that in the stroma around the intact glands and dysplastic changes (p < 0.05). All the study groups showed a membrane reaction with E-cadherin and beta-catenin, which probably suggested that changes were absent in the Wnt signaling pathway. In 70.2% of invasive adenocarcinomas, laminin demonstrated a significant cytoplasmic expression in 5-30% of the tumor cells predominantly located along the tumor invasion area or in the deepest tumor complexes (p > 0.05). CONCLUSION: CD44 and tenascin are of great diagnostic value in examining invasive and microinvasive adenocarcinomas of the cervix uteri. E-cadherin and beta-catenin are of no diagnostic value in the study groups of pathological processes. Laminin is a potential marker of stromal invasion; however, its expression calls for further investigation.

[Differential diagnosis of precancerous and regenerative changes in the epithelium of the cervix uteri, by applying an immunohistochemical study].

UNLABELLED: Precancerous changes in the epithelium of the cervix uteri include low- and high-grade squamous intraepithelial lesions (LGSIL and HGSIL). Morphologically, these must be differentiated, among other conditions, immature squamous metaplasia (ISM) of the cervix uteri. MATERIALS AND METHODS: This study involved 119 cases divided into 3 groups: 1) LGSIL (n = 28); 2) HGSIL (n = 56); 3) ISM (n = 35). An immunohistochemical study was conducted using antibodies to p16INK4a, CK17, and Ki-67 according to the standard protocol. RESULTS: Ki-67 expression was mainly low and moderate in 67.9% of cases in the LGSIL group; it was seen in 100% of cases in the HGSIL group, being significant in 73.5%. In the ISM group, Ki-67 was identified in 65.7% of cases, most of which demonstrated a low-to-moderate expression. In the LGSIL group, the expression of p16INK4a was recorded in 46.4% of cases. In the HGSIL group, the reaction was observed in 73.2% of cases; of them 57.2% it was strong. In the ISM group, the reaction was chiefly low in 38.6% of cases. In the LGSIL group, CK17 expression was found in 17.9% of cases. In the HGSIL group, the reaction was recorded in 19.7% of cases, the expression being predominantly low. In the ISM group, the marker was detectable in 88.5% of cases; of them 51.4% showing a high expression. The expressions of p16NK4a and Ki-67 were statistically significantly higher in the HGSIL group (p < 0.05) than those in the LGSIL and ISM groups. On the contrary, the expression of CK1 7 was significantly higher in the ISM group (p < 0.05) than in the HGSIL and LGSIL groups. Thus, evaluation of p16INK4a, Ki-67, and CK17 expressions is a valuable diagnostic tool in the differential diagnosis of HGSIL, LGSIL, and ISM.

[Cellular pathology and revolution of scientific medicine (on the occasion of the 190th anniversary of Rudolf Virchow's Birth)].

Rudolf Virchow destroyed the old humoral pathology, created the doctrine of cell physiology and pathology, which has not lost its importance to date, described a great many pathological processes in detail, and put into practice appropriate terminology and classification. Up until the present pathology appreciably remains Virchow's cellular pathology despite modern science advances, inevitable changes and clarities of our ideas about the structure and function of organs and tissues. Virchow's cellular pathology has radically altered the view on the essence of painful processes, by opening a new epoch in the history of medicine and medical science.

[Prognostic factors of renal cell carcinoma].

The crucial predictor of renal cell carcinoma (RCC) is a clinical stage, although the significance of this parameter isn 't confirmed for all histological types of carcinomas. It remains unknown what factors ensure the sensitivity of the tumor to chemotherapy and why metastasis is accompanied by the development of resistance to therapy. The data about the prognosis of RCC rare variants are extremely scarce. Ubiquitin-dependent proteolysis plays an important role in the development of RCC, but the prognostic significance of this signal way's proteins is poorly understood. In order to find out significant factors for prognosis of RCC clinical course it's necessary to use the complex spectrum of tumor growth regulation factors and genetic tests.

[Glandular lesions of the cervix].

In the review the most abundant types of cervical glandular lesions including precancerous lesions and benign hyperplastic, metaplastic and ectopic changes are considered. The most popular classifications, their advantages and disadvantages, morphological criteria, and the principles of differential diagnosis are discussed. The basic areas of an immunohistochemical study and the specific features of different markers expression used for differential diagnosis are covered.

[Logistic support and ways for reducing costs in a pathological laboratory].

The paper provides a comparative technical-and-economical assessment of the basic reagents that are most commonly used for histological processing of tissue specimens in terms of cost optimization. The presented data may be useful to experts to make decisions on the current logistical support of pathology laboratories.

[Impact of technical characteristics of histological equipment on the research costs].

The paper provides a comparative technical-and-economical assessment of manual and hardware-based methods for histological tissue processing in terms of cost optimization. The presented data may be useful to experts to make decisions on the logistical support of pathology laboratories.

[Current views of the molecular mechanisms of gastric cancer progression].

The available technologies have expanded our knowledge about the mechanisms of oncoprogression. Studies of the Wnt signaling pathway in the neoplastic cells could identify new promising markers in assessing the course and prognosis of this disease. beta-catenin as a key protein of the Wnt pathway is involved in the regulation of tumor proliferative activity and in the processes of epithelial-mesenchymal transformation, by regulating E-cadherin metabolism and affecting the close contacts of the gastric epithelium. A competitive interaction between P-cadherin and beta-catenin without forming reasonably close contacts is another cause of impaired intercellular interactions and tumor metastases. Claudin-1 expression in the tumor pool as a marker of invasion requires further investigations. Traditional markers of proliferation and apoptosis, such as Ki-67, p53, and bcl-2, may be further used to estimate the rate of tumor growth.

[Logistic support and means for reducing the current costs in a pathology laboratory].

The basic reagents that are most commonly used for histological tissue specimen treatment have undergone technical-and-economic assessment in terms of cost optimization. The presented data may be useful for experts to make decision on the current logistical support of pathology laboratories.