[Hormone therapy alone for pre-cancerous conditions and early endometrial cancer: pros and cons].

The results of conservative treatment of 121 patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) with preservation of fertility are presented. In EAH (n = 56) for 6 months the intrauterine spiral Mirena was used. The effectiveness was 91%, the recurrence rate 16%, pregnancies occurred in 16% of patients. In EC (n = 65) hormone therapy was conducted for 6 months using the intrauterine spiral Mirena and zoladex. The effectiveness was 79%, recurrence rate 22%, pregnancies occurred in 24% of patients. Based on our data and on the results of other studies, the benefits and risks of hormone therapy alone for EAH and EC are discussed in women of reproductive age.

[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.

[Key enzymes of degradation and angiogenesis as a factors of tumor progression in squamous cell carcinoma of the cervix].

A key role in tumor progression play two processes--the destruction and angiogenesis. Matrix metalloproteases (MMPs) play a leading role during tissue degradation. Tissue collagenase--MMP-1 and MT1-MMP hydrolyze fibrillar collagens, which are the basis of connective tissue matrix, and ensure the development of an invasive process. Gelatinase A and B (MMP-2 and MMP-9) hydrolyze collagen type IV, which is the basis of the basal membrane, and facilitate the development of metastasis. Endogenous tissue inhibitors TIMP-1 and TIMP-2 are involved in the regulation of MMP expression and activity. It has been established that MMP-9 release vascular endothelial growth factor (VEGF) associated with the STM--the primary inductor angiogenesis. Angiotensin-converting enzyme (ACE) participates in the induction of VEGF synthesis. ACE--a key enzyme of the renin-angiotensin system, forms angiotensin II, which interactes with the receptor ATIR and induces VEGF synthesis, as well as stimulates endothelial cell proliferation. Our experimental studies devoted to the study of particularity expression of key enzymes of destruction and angiogenesis in squamous cell carcinoma of the cervix (SCC). It was studied: MMP-1, MT1-MMP, MMP-2 and MMP-9 and their endogenous regulators: TIMP-1, TIMP-2, and as well as ACE. Work was performed on clinical specimens containing the tumor tissue, taking into account the presence or absence of metastasis to regional lymph nodes and the specimens of adjacent morphologically normal tissue. It was shown that the increase of MMP-1, MT1-MMP and MMP-9 expression and low of TIMP-1 and TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. The change of MMP-2 expression is not so significant and it is less influenced to the destructive potential. It was shown dramatic increasing of MMP-1 and MMP-9 activity in metastasizing tumor tissue ACE activity in a tumor in most of the samples was higher than the activity in normal tissues. It was established that the expression of key enzymes degradation and angiogenesis occurs not only in tumor but also in normal tissues. Data are important for understanding the mechanisms of tumor progression and have prognostic value and may affect the therapeutic strategy for patients.

[Comparative study of the determination of the HER2 status in gastric cancer in the biopsy and intraoperative specimens].

OBJECTIVE: To determine the HER2 status of gastric adenocarcinomas, by using biopsy and intraoperative specimens. SUBJECTS AND METHODS: Immunohistochemistry and in situ hybridization were used to examine the HER2 status of 346 gastric cancer biopsy and intraoperative specimens. RESULTS: The study conducted on a large Russian sample of 346 patients showed a positive HER2 status in 10.7% of the examined specimens. Intestinal-type adenocarcinomas exhibited a positive HER2 status in 21.4% of the cases. Comparative analysis of the HER2 status in the biopsy and intraoperative specimens indicated that there were differences in the determination of the tumor HER2 status in less than 1% of the examined specimens. The remaining found differences (14.7%) failed to change the tumor HER2 status and to affect the choice of a treatment regimen. CONCLUSION: The performed investigation has demonstrated that the tumor HER2 status determined in the biopsy specimen significantly reflects the molecular biological properties of gastric cancer and may be clinically used to determine indications for the use of targeted drugs.

[Metanephric adenoma of the kidney].

The paper describes metanephric adenoma, a rare adenoma, diagnosed in a patient 20 years after surgery. It provides a histological description of the tumor and a concise review of the literature.

[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.

[New aspects of the pathogenesis and classification of basal-like breast carcinoma].

New approaches to the molecular classification of breast cancer are considered. Particular emphasis is placed on its basal-like type that belongs to the most aggressive and prognostically unfavorable forms of tumor. The origin of this type of breast cancer is the subject of intense debate in the scientific community. There are three basic theories that basal-like breast carcinoma may arise from the stem or myoepithelial cells and through dedifferentiation via epithelial-mesenchymal transformation. The theory of its origin from stem/progenitor cells is most valid and proven.

[Allelic imbalance in patients with non-small cell lung cancer].

Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers and is characterized by multiple genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of the study was to analyze of molecular-genetic alterations in tumor and tissue surrounding the tumor to determine genetic features of different histological types of NSCLC and its possible associations with clinicopathological parameters of patients. A microsatellite analysis of chromosomal regions 12p23.3, 2q35, 3p14.2, 3p22.2, 3p26.3, 9p22.1, 17p13.3 was performed. The frequency of genetic alterations in NSCLC was 50% in average. LOH/MSI in the tumor surrounding tissue at 2 and 5 cm. from tumor was not detected. There were statistically significant associations between LOH and/or MSI and the tumor stage, its histological type and smoking status. The found genetic alterations can be used as molecular markers of squamous cell lung cancer in difficult diagnostic cases and appraised as prognostic markers.

[WHO classification of tumors of the breast, 2012].

The classification of tumors of the breast was revised and considerably modified in 2012. The main modifications were applied to epithelial tumors. The clinical types of breast cancer were identified. These were inflammatory and bilateral carcinomas. No substantial amendments were made in the classification of mesenchymal tumors. This paper discusses the new WHO classification of tumors of the breast, 2012, by describing the histological forms and immunohistochemical profile of neoplasms in detail. Its dissimilarities from the previous edition are given. The systems for evaluating medical pathomorphism are detailed.

[Interstitial collagenase, gelatinases A and B and their endogenous inhibitors in squamous cell cervical carcinomas].

Interstitial collagenase and gelatinases are matrix metalloproteinases (MMP), which play the key role in tumor invasion and metastasis. The aim of this study was to elucidate the peculiarities of expression of interstitial collagenase (MMP-1), gelatinases A and B (MMP-2 and MMP-9) and their endogenous tissue inhibitors TIMP-1 and TIMP-2 as invasive factors of squamous cell carcinomas (SCC) of human cervical cancer. The study was carried out using 24 specimens of SCC and 11 specimens of adjacent to tumor morphologically normal tissue. All carcinoma specimens expressed E7 HPV-16 gene. It was shown that the increase of MMP-1 and MMP-9 expression and low of TIMP-1 and TIMP-2 expression makes the main contribution to the destructive (invasive) potential of SCC. The change of MMP-2 expression is not so significant and it is less influenced to the destructive potential. Moreover, substantial expression of MMP-1, MMP-2 and MMP-9 was registered in the specimens of morphologically normal adjoining to tumor tissue. This expression was found to make an additional contribution to the destructive potential of cervical tumor.

[Experimental validation of the use of ND:YAG-interstitial laser coagulation of the kidney].

Interstitial laser coagulation (ILC) is one of the effective methods of minimally invasive destruction of small renal tumors. For the safe use of ILC in clinical practice, it is necessary to select the optimal mode of action of laser radiation on the tissue of target organ and techniques for the procedure. The effects of ILC on kidney tissue in 6 rabbits weighing less than 3 kg and 5 mongrel dogs weighing up to 20 kg were investigated in vivo. The impact of ILC was made intraoperatively. Organ retrieval in experimental animals for the macro- and microscopic examination was performed immediately after the impact of ILC and at various times thereafter during the month in rabbits and 35 days in dogs. Morphological study in different periods after exposure allowed to establish phasing and volumes of changes in the tissues of the kidney, confirming the safety and efficacy of ND:YAG laser irradiation on kidney tissues. The results indicate the possibility of effective application of ILC of kidney tissues for destruction of small size tumors, without impairment of functions of the organ.

[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.

[Determination of the possibilities of targeted therapy for gastric cancer].

The objective of the investigation whose results are given in the paper was to compare a few HER2 testing techniques (immunohistochemistry, fluorescence in situ hybridization, and silver in situ hybridization) for adenocarcinomas of the stomach and esophagogastric junction. Different antibody clones and in situ hybridization kits were comparatively analyzed. Recommendations for the use of different testing methods and for the interpretation of their results are given.

[Allelic disbalance in 1q32 area and microsatellite instability renal papillary adenocarcinoma].

Papillary adenocarcinoma is an abundant form of renal cell carcinoma. At present any diagnostic and prognostic molecular markers of papillary adenocarcinoma are absent, however some cytogenetic and molecular-genetic features of disease are known. According to literary data, the 1q32 duplication is associated with progressive deterioration of primary tumor. We have done a genetic typing (D1S2142 and D1S3465 locus) of 39 papillary adenocarcinoma cases, used PCR and fragment analyses of the 1q32 area. Frequency of the allelic disbalance was 36.8%; the microsatellite instability was found out in 48.7% of cases. The association of genetic disturbances with clinic-morphological features of papillary adenocarcinoma wasn't revealed. In some cases genetic heterogeneity of tumor-adjacent renal parenchyma and primary tumors was found out at multifocal renal carcinoma. For the first time we ve demonstrated that the allelic disbalance in 1q32 area and the microsatellite instability are frequent molecular-genetic disturbances in sporadic papillary carcinomas at all stages of the disease. Probably, the microsatellite instability is connected with progressive deterioration of primary tumor at renal papillary adenocarcinoma.

[Prostate biopsy in the outpatient setting].

The article describes the methodology of transrectal diagnostic prostate biopsy under ultrasound guidance with regard to settings of municipal polyclinic; existing complications are listed. The analysis of the results of 876 biopsies performed within 3 years is presented. The distribution of the results of histological examination depending on the level of total PSA, ratio of free and total PSA, and PSA density was followed-up. Relationship between PC detection rate using standard biopsy and prostate volume is shown. The analysis of the degree of PC differentiation (Gleason score) depending on the level of total PSA, the ratio of free and total PSA, and PSA density was performed. Practical recommendations to improvement of PC detection rate are presented. Based on the analysis, it was concluded that the screening for prostate cancer for the purpose of its earlier diagnosis is reasonable.

[Benign metastatic leiomyoma of the corpus uteri].

Benign metastasizing leiomyoma (ICD.0 8898/1) is a rare phenomenon characterized by multiple benign smooth muscle tumors (metastases) in the organs and tissues of patients with uterine leiomyoma without evidence for another tumor process. This tumor should be differentiated from leiomyosarcoma, at the same time account must be taken of the fact that its morphological criteria are not always effective. Molecular genetic testing is a more accurate method that allows valid differentiation of leiomyoma from leiomyosarcoma. Genetic testing is used to estimate losses of heterozygosity and microsatellite instability, which are characteristic of leiomyosarcoma only. The paper describes a clinical case of benign metastasizing leiomyoma in a 54-year-old patient with uterine myoma and pelvic lymph node metastasis. Molecular genetic testing was carried out using the samples obtained from primary uterine leiomyoma, morphologically altered ovarian tissue, and lymph node metastasis to determine the common origin of tumors in the uterus and lymph node and to reveal the benign or malignant nature of these neoplasms. Despite the fact that the term "benign metastasizing leiomyoma" is widely accepted in the world literature, neither these tumors nor metastases have morphological or genetic signs of malignancy so we consider the term "systemic leiomyomatosis" to better reflect the essence of this process.

[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.

[Clonal origin of multiple foci of urinary bladder cancer].

To analyze the pattern of molecular damages in urinary bladder cancer (UBC), the authors studied allelic imbalance of chromosome loci 9p21 and 17p13 in 22 patients diagnosed as having multiple primary UBC (2 to 5 foci in each patient). The state of markers has no informative value in 3 (13.6%) cases; in 9 (47.4%) of 19 informative cases, deletion of the same allele was determined in at least one of the loci in question in all tumor nodules, which may point to the monoclonal origin of multiple tumors in these patients. Five (26.3%) of the 19 patients exhibited deletion of the same allele in different tumor nodules, which is suggestive of the active process of clonal evolution and the feasibility of tumor subcloning, which does not preclude the possibility of monoclonal origin. Five (26.3%) of the 19 patients had an imbalance of different alleles in varying nodules, which may show the oligoclonal origin of the tumor nodules concerned. The concordant and discordant patterns of molecular damages are encountered virtually with the same frequency in the tumors of multiple primary UBC, which supports the view that its synchronous tumors can develop both monoclonally through intraluminal dissemination of tumor cells and when there are cancerization fields that determine the occurrence of oligoclonal tumors.