[Morphological evidence of the ischemic nature of the prostatic fibrosis in the classical chronic pelvic pain syndrome / IIIB chronic prostatitis].

AIM: To examine the structure of the prostate tissue in patients with III B chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). MATERIALS AND METHODS: The study analyzed transrectal fine-needle biopsy specimens of 10 patients with the verified diagnosis of chronic pelvic pain syndrome/category III B chronic prostatitis (CPPS/IIIB CP) according to the National Institutes of Health classification. Tissues were examined using light and electron microscopy, and immunohistochemical study of the expression of CD31, CD34, NSE and S-100 markers. RESULTS: All biopsy specimens of all patients showed fibroplastic changes of the prostate tissue most markedly pronounced in the stroma and muscle fibers in the form of total fibrosis, myofibril atrophy, and extracellular lipofuscin deposition. The examination revealed a significant reduction in the density of microcirculatory bed vessels and arteriolar luminal stenosis, a reduction in the number of nerve fibers, and compression of their fibrous tissue. No inflammatory changes were found in the prostate. DISCUSSION: In patients with CPPS/IIIB CP, the changes in the prostate at the microscopic and ultrastructural levels are characteristic of severe chronic tissue hypoxia, which leads to the development of fibrosis resulting in stenosis of microcirculatory bed vessels and degenerative changes in nerve fibers and cells. No signs of an inflammatory reaction in the examined tissue were established. CONCLUSION: Changes in the prostate tissue in CPPS/IIIB CP suggest the presence of chronic pelvic ischemia and exclude its association with inflammation as the main pathological process.

[Connexin 43 expression in human brain glial tumors]. / Ékspressiia konneksina 43 v glial'nykh opukholiakh golovnogo mozga cheloveka.

AIM: Тo conduct an immunohistochemical (IHC) study of the expression of connexin 43 in the samples of glial tumors of various grades: gemistocytic astrocytomas (Grade 2), oligodendrogliomas (Grade 2) and glioblastomas (Grade 4). MATERIAL AND METHODS: The material investigated was fragments of human brain glial tumors (grade 2 gemistocytic astrocytomas (n=2), grade 2 oligodendrogliomas (n=2), and grade 4 glioblastomas (n=14) and those of tumor-surrounding tissue (n=4). The material was fixed in 10% buffered formalin, dehydrated, and embedded in paraffin according to the standard technique. IHC studies of the slices applied primary rabbit polyclonal antibodies against connexin 43 ('Spring Bioscience', USA) and the Dako EnVision + Peroxidase (DAB) visualization system ('Dako', Denmark). After the immunohistochemical reaction, the cell nuclei were stained with Mayer's hematoxylin. RESULTS: Immunohistochemistry showed the changing pattern of connexin 43 expression as compared with intact tissue in the glial tumors. Instead of the fine-granular expression in the thin cellular processes in the neuropil, the tumors mainly displayed a coarse-grained cytoplasmic and even nuclear reaction. The morphology and localization of positive structures depended on the variant of an examined tumor. In addition, the most malignant brain gliomas generally exhibited a reduction in the expression of connexin 43, i.e. its quantity is inversely proportional to the degree of malignancy of the tumor. CONCLUSION: The low connexin 43 expression levels may reflect both a reduction in astroglial functional gap junctions and semicanals and a decrease in the amount of the protein itself that has independently antioncogenic properties. The observed cytoplasmic and nuclear expression of connexin 43 is most likely to be associated with the aberrant activity of a number of kinases, such as proto-oncogene tyrosine-kinase Src or protein kinase C (PKC).

[Ultrastructural characteristics of gap junctions in human glial brain tumors]. / Ul'trastrukturnaya identifikatsiya shchelevykh kontaktov v glial'nykh opukholyakh golovnogo mozga cheloveka.

AIM: to conduct an electron microscopic study of intercellular communication in the samples of gemistocytic astrocytoma, oligodendroglioma, and glioblastoma. MATERIAL AND METHODS: Surgically resected tumor tissue fragments were fixed in 2.5% glutaraldehyde solution, afterfixed in 1% OsO4 solution, dehydrated, and embedded in epoxy resin. Ultrathin sections were examined using a Jem 1011 electron microscope (Jeol, Japan). RESULTS: Solitary and closely spaced gap junctions (GJs) formed by the thin processes that have the ultrastructure of an astroglial processes were identified in the astrocytoma samples. In this case, chemical synapses were noted to be completely absent in gemistocytic astrocytoma and glioblastoma. The identified GJs had a small length and deformed nexuses. The oligodendroglioma samples exhibited intact astroglial processes around the chemical synapses; however, interglial GJs were not found. CONCLUSION: The investigation showed the presence of intercellular GJs with some ultrastructural differences in the samples of low- and high-grade astroglial tumors. According to current data, astrocytomic GJs are able to create a stable self-sustaining network that promotes tumor progression and provides resistance to a therapeutic intervention. At the same time, the noticeable reduction in the number of GJs, which is most pronounced in the oligodendroglioma sample, can accelerate tumor cell migration into the surrounding parenchyma. The investigation of GJs should be, of course, continued using a group of a larger number of glial tumors to confirm the intercellular communication features revealed in this study.

[PECULIARITIES OF THE STRUCTURAL ORGANIZATION OF VENTRAL POSTEROMEDIAL, VENTRAL POSTEROLATERAL, AND RETICULAR NUCLEI OF RAT THALAMUS (AN IMMUNOHISTOCHEMICAL STUDY)

The aim of this work was an immunohistochemical study of the expression of neuronal and glial proteins, and of gap junctions proteins (connexin 36, connexin 43) in ventral posteromedial (VPMN), ventral posterolateral (VPLN) and reticular (RТN) nuclei of the thalamus in rats. It was found that VPMN and VPLN of the thalamus were characterized by a homogeneous distribution of synaptophysin, grouped arrangement of astrocytes, horizontal orientation of somatostatincontaining myelinated and unmyelinated nerve fibers, forming the bundles, and running through the barreloid septum, expression of connexin 36 and 43 as well as of parvalbumin revealing barreloids in 4 µm-thick sections. In RTN the content of myelin basic protein, neurofilaments, parvalbumin, and somatostatin was increased, while the amount of glial fibrillary acidic protein and connexin 43 was moderate, and synaptophysin and connexin 36 were absent.

[Numerical impairments in genes in breast cancer: a multiplex ligation-dependent probe amplification study].

OBJECTIVE: To analyze breast cancer samples using the new technique multiplex ligation-dependent probe amplification (MLPA) assay. MATERIAL AND METHODS; Formalin-fixed paraffin-embedded breast carcinoma samples from 65 patients were examined. After manual microdissection, DNA was isolated using a commercial kit ("QIAGEN") and analyzed with SALSA MLPA KIT P078-B1 Breast Tumour ("MRC-Holland"). Capillary electrophoresis provided results. RESULTS: MLPA assay was successful in all examined samples. The amplification and deletion frequencies of the analyzed genes were in line with the literature data. The technique requires conventional work-related skills in a molecular genetic laboratory and, as a whole, presents no problems with its usage. The interpretation of results is devoid of subjective meaning due to exclusively their mathematical analysis. MLPA assay provides an insight into numerical impairments in the following genes: ERBB2, MYC, TRAF4, C11orf30 (EMSY), ADAM9, IKBKB, CCNE1, TOP2A, CDH1, CDC6, ESR1, CPD, EGFR, MTDH, CCND1, BIRC5, MED1, FGFR1, MAPT, PRDM14, and AURKA. CONCLUSION: MLPA is an easy-to-use and promising method for multiplex genetic analysis of tumor cells in breast cancer.

[Specific features of gene amplification on the long arm of chromosome 17 in different molecular genetic subtypes of breast cancer].

The frequency of gene amplification and coamplification of HER2/neu, TOP2A and the centromeric region of chromosome 17 (CEP17) was examined in 265 breast cancer (BC) cases belonging to different molecular genetic subgroups. Luminal B breast cancer was found to be characterized by the increased probability of coamplifications (CEP17 and HER/neu, HER2/neu, and TOP2A) on chromosome 17. At the same time, the amplification of just three loci on one chromosome is a rare event and encountered in 17% of luminal B breast cancer cases (or 1.1% of all BC cases). That of HER2/neu in conjunction with elevated CEP17 count is statistically significantly more rarely accompanied by deletion of TOP2A rather than its amplification. The findings suggest that there are different amplification mechanisms in different BC molecular genetic subgroups.

[Molecular genetic study of B- and T-lymphocyte clonality in the diagnosis of non-Hodgkin's lymphomas].

The value of molecular genetic methods in the current diagnosis of lymphoproliferative diseases is estimated. A standardized BIOMED2 protocol for these studies is described. The merits and demerits of this method are considered.

[Different Her-2 status in infiltrative and intraductal components of the breast cancer].

In the article a breast cancer case with different Her2 status in invasive and non-invasive components is described. We emphasize on the importance of knowledge about tumor histology for correct interpretation of FISH Her2-test results.

[HER-2/neu-testing in breast cancer: is the immunocytochemistry competent?].

According to ASCO/CAP guidelines, there are two recommended methods for Her2/neu-testing in breast cancer patients such as immunohistochemistry and fluorescence in situ hybridization. This paper analyses results of alternative immunocytochemical method for Her2/neu detection and its diagnostic pitfalls.

[10 years of testing of the HER2 status in breast cancer in Russia].

The paper analyzes 10 years' experience in HER2 status testing in breast cancer in Russia. The ASCO/CAP HER2 testing guidelines adaptable to the work of pathologists in Russia are considered.

[The first experience of external quality control of immunohistochemical studies in the diagnosis of lymphoproliferative diseases].

The paper presents the results of estimating the quality of immunohistochemical (IHC) staining in 36 pathologic laboratories of the Russian Federation. The results of IHC stains were assessed in 17 markers (CD3, CD5, CDIO, CD15, CD20, CD23, CD30, Bcl2, Bcl6, Pax5, TdT, Mum1, Cyclin D1, Ki-67, Kappa, Lambda, ALK), which are frequently used in the diagnosis of lymphoproliferative diseases, in the sections of specially formed tissue matrices. The study conducted in most participating laboratories has revealed the considerable IHC staining technology flaws that can critically affect the quality of diagnosis of lymphoproliferative diseases; the diagnostic capacities of some participating laboratories are inconsistent with the solved problems for a number of key antibodies being unavailable.

[Role of chorioamnionitis in the development of sepsis during labor].

The authors emphasize the importance of pyoseptic diseases of the reproductive system, which are a major cause of maternal mortality. Clinical and morphological criteria have been elaborated to diagnose a special form of obstetric sepsis during labor. The inflammatory infiltrate was investigated by immunohistochemical studies using monoclonal antibodies and tumor necrosis factor. Lesions of the fetal integument and placenta have been found to be an initiating factor. The fetal integuments with signs of chorioamnionitis serve as the entry of pathogens during the septic process, promoted the development and course of septicemia during labor and complications, such as disseminated intravascular coagulation and infectious-toxic shock.

[Clinical and morphological features of labor sepsis as an independent nosological entity].

Examination of 15 autopsies of puerperas who died in the first postpartum days has identified the pathomorphological and immunohistochemical signs differentiating labor sepsis from the other type - postpartum sepsis. Labor sepsis that runs typically of a systemic inflammatory reaction is characterized by initial antenatal inflammation of the fetal membranes and placenta with the latter's immunoimaging of granulocytes, macrophages, plasma cells, and tumor necrosis factor. Moreover, labor sepsis runs in the presence of suppressed cellular and humoral immunity in the spleen and lymph nodes. The relative intact pattern of the uterine endo- and myometrium is retained with generalization of an inflammatory reaction along the organs. The pathologist who analyzes female pyoinflammatory diseases in the postpartum period should meticulously investigate all placental components in addition to a puerpera's organs.

[Morphological characteristics and intracellular electrolytic composition of blood cells at surgeries on lower extremities arteries].

Morphological characteristics and trace and macroelement composition of blood cells flowing out of ischemic lower limb before, during and after reconstructive surgeries under different type of anesthesia. A total of 102 male patients aged 45 to 60 years with atherosclerotic occlusions of the arteries of the femoral-popliteal zone were included into the study. According to anesthesia type all the patients were divided into 3 groups: group 1 consisted of 34 patients operated under spinal anesthesia, 37 patients of group 2 underwent surgery under combined anesthesia (spinal anesthesia with intravenous sedation), 31 patients of group 3 - under total intravenous anesthesia with myoplegia and artificial pulmonary ventilation. All the blood examinations were carried out with scanning electron microscope XL-30 ("Philips") and X-ray spectrum microanalyzer Edax ( "Edax International", USA). It is demonstrated that in spinal and combined anesthesia morphological characteristics of blood cells normalized due to optimization of intraerythrocytic and intrathrombocytic electrolytic homeostasis unlike total intravenous anesthesia, when intracellular imbalance of trace and macroelements progresses and ultrastructural cellular alterations persist.

[Pathomorphology of adenohypophysis in cases of massive obstetric hemorrhages (morphometric and immunohistochemical studies)].

There have been performed morphometric and immunohistochemical examinations of adenohypophysis of 15 females who died of massive post-partum hemorrhages. The revealed changes in the form of hypertrophy of the basophilic cells are the initial stages of Sheehan's syndrome developing as a result of long-term progression of hypopituitarism. Massive obstetric bleeding causes severe complications-posthemorrhagic shock, the pathogenetic mechanism of which includes necrosis of the cells in the anterior part of the hypophysis. Cause-effect relations were shown for the amount of the post-partum blood loss and the revealed pathomorphologic changes in the hypophysis. Hyperproduction of ACTH by the basophilic cells of the adenohypophysis revealed by immunohistochemical analysis is a compensatory mechanism under the conditions of acute adrenal insufficiency inherent in any shock including posthemorrhagic.

[Clinical significance of histological types of prostatic cancer]. / Klinicheskoe znachenie gistologicheskykh tipov raka predstatel'noi zhelezy.

Biopsy material obtained from 310 patients with prostatic cancer (PC) was used in the study of the incidence rate of different PC histological types, of tumor cell immunophenotype and differentiation by Glison. The results of the study have shown that definition of the tumor histological type and tumor immunophenotype facilitates identification of tumors with the most malignant potential. Therefore, this definition should be included into the diagnostic complex in the study of PC. Choice of treatment policy should not be based only on differentiation of the tumor process by Glison. The decision should be made only after establishment of histogenesis and immunophenotype of tumor cells. The presence of neuroendocrine differentiation is an unfavourable prognostic factor.

[Kidney carcinosarcoma]. / Kartsinosarkoma pochki.

A kidney tumour in a 36 year old female is described. The tumor was soft, of gray-brown color, size 12 x 11 cm. Histological, immunohistochemical and ultrastructural findings have demonstrated the signs of biphasic epithelial and mesenchymal cell differentiation. These data allowed the authors to define this tumor as a renal carcinosarcoma. Histogenesis of this tumor and differential diagnosis with other malignant renal tumors are discussed.

[Current status and trends in the development of medical information systems for morphological research]. / Sostoianie i tendentsii razvitiia meditsinskikh informatsionnykh sistem dlia morfologicheskikh issledovanii.

The time of cooperative action of the information medical systems is coming. Standardization of clinical laboratory information systems is one of the most difficult but important problems for clinical laboratory community and technicians. Electronic data exchange requires agreement on the data element format by which healthcare institutions can exchange. Computerization of health care service raises the problem of security because the risk of violation of medical privacy is dramatically increasing. Unauthorized users can access, copy, alter, delete or distort hundreds or thousands of medical records within minutes. Information can be faulted by individuals or system failure. It is necessary to discuss and make a final decision of joining some standard for the purpose of integration.