Mast Cells in Renal Cancer: Clinical Morphological Correlations and Prognosis.

Morphofunctional activity of mast cells in renal cancer is studied on specimens from the center of the tumor, peritumorous zone (with an obligatory fragment of the pseudocapsule), and from renal tissues maximally distant from the tumor. The counts and areas of tumor cells were maximum in the peritumorous zone in comparison with intact kidney tissue and central zone of the tumor. Analysis of correlations revealed a direct correlation between the tumor cell count in the peritumorous zone and some clinical morphological parameters of the tumor (anaplasia degree, size, presence of invasion and metastases, and angiogenesis). The count of mast cells in the renal peritumorous zone inversely correlated with 5-year survival: 100% cumulative 5-year survival in patients with mast cell count <6.7±1.6 per field of view.

Expression of B23/Nucleophosphamine Nonribosomal Nucleolar Protein in Smooth Muscle Tumors of the Corpus Uteri.

Immunohistochemical study of B23/nucleophosmine (NPM), the key argyrophilic nonribosomal protein associated with the nucleolus-producing regions, in smooth muscle formations of the body of the uterus and myometrium was carried out. The uterus index, number of positively stained nucleoli in the nucleus, integral optical density, and area of positively stained nucleoli were studied by computer-aided image analysis. The results indicated significant differences in the integral optical density and less so in the areas of NPM+ nucleoli in leiomyosarcomas, but not in intact myometrium and leiomyomas. Coefficients of variations in the integral optical density and NPM area proved to be significant parameters for differentiating leiomyosarcomas by size (≤7 cm or larger), evaluating the malignancy grade and stage of the process. NPM parameters in leiomyomas and leiomyosarcomas differed significantly, depending on the levels of Ki-67 and p53 expression and the receptor status of leiomyosarcoma. The index of area and the integral optical density of NPM could serve a accessory objective differential diagnostic criteria in cellular and mitotically active liomyomas and well-differentiated leiomyosarcoma of the corpus uteri.

[Non-small cell lung cancer: HER2 oncogene status].

OBJECTIVE: to study HER2 protein and HER2 gene, their heterogeneity in non-small cell lung cancer. MATERIAL AND METHODS: 218 intraoperative non-small cell lung samples were examined using tissue matrix methods. HER2 protein was determined by immunohistochemistry (clone 4B5, <> and HER2 gene and CEP1 7 were evaluated by in situ hybridization (SISH, <>). RESULTS: Positive and indefinite statuses were found in 59 (27%) and 47 (22%) cases, respectively; intratumor heterogeneity was detected in 32 (30%) cases. Amplification of the HER-2 gene was found in 12 (6%) cases; that of the HER2 gene along with an increase in CEPI 7 was observed in 7 (3%) cases; elevated CEP1 7 levels were seen in 19 (9%) cases. Intratumor heterogeneity of HER2 gene amplification was not found; however, one case of adenocarcinoma showed high-level HER2 gene amplification in the gland-like areas and low-level HER2 gene amplification in the solid areas. HER2-positive status and amplification were more common in adenocarcinoma than in squamous cell carcinoma (p<0.001). There was a moderate correlation between HER2 immunohistochemical status and amplification (r=0.38; p<0.001). CONCLUSION: Thus, in non-small cell lung cancer, there is an elevated HER2 protein level and, well less frequently, altered activity in the HER2 gene (amplification) as a cause of enhanced protein synthesis.

Argyrophilic proteins of nucleolar organizer regions and proliferative activity of cells in squamous cell carcinoma of the lung.

Argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins) and Ki-67 antigen were analyzed in 118 samples of squamous cell carcinoma of the lungs. Tumors with low and high content of Ag-NOR proteins and Ki-67 index were selected. It was found that the content of Ag-NOR proteins correlated with some clinical and morphological parameters (indexes T and N, tumor size less and more that 3 cm, stage of the disease, and tumor differentiation degree) and survival rate. High survival was associated with low content of Ag-NOR proteins and Ki-67 index and low survival correlated with high content of Ag-NOR proteins and Ki-67 index, while intermediate survival was associated with opposite values of Ag-NOR protein content and Ki-67 index. The tumor size, parameter N, and the content of Ag-NOR proteins had independent effects on patient's survival. In patients with squamous cell carcinoma of the lung without metastases in lymph nodes, survival correlated with the content of Ag-NOR proteins; in patients without metastases, survival correlated with tumor size.

[Topoisomerase IIa expression in correlation with clinical and morphological parameters and proliferation (based on argyrophilic proteins of nucleolar organizer regions and Ki-67 antigen) in lung adenocarcinoma].

Investigated topoisomerase IIalpha (TopoII alpha), argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR) and antigen Ki-67 in lung adenocarcinoma. Defined tumor with low and high TopoII alpha, Ag-NOR and Ki-67. TopoII alpha had a relationship with clinical and morphological parameters (greatest dimension, tumor differentiation) and proliferation markers (Ag-NOR, Ki-67) . Survival of patients with lung adenocarcinoma with low content of TopoII alpha is better as compared with high content of TopoII alpha. Survival of patients with lung adenocarcinoma depends on the mutual content of TopoII alpha and clinical and morphological parameters (value T, greatest dimension, value N, stage, tumor differentiation), proliferation markers (Ag-NOR). TopoII alpha content in lung adenocarcinoma is an independent prognostic factor. Mutual research of TopoII alpha with clinical and morphological parameters and Ag-NOR has prognostic value in lung adenocarcinoma.

Relationship between the argyrophilic proteins of the nucleolar organizer region and stage of squamous-cell carcinoma of the lung.

Argyrophilic proteins associated with chromosome nucleolar organizer regions (Ag-NOR proteins) were studied in lung squamous-cell carcinoma cells. After routine staining with silver nitrate, the area index and coefficient of variations of Ag-NOR protein were estimated by computer-aided image analysis. The Ag-NOR protein area indexes of tumor cells differed in clinical morphological variants of squamous-cell cancer (differing by T and N parameters, size of the primary node <3 cm or larger, by disease stage, and differentiation degree). Ag-NOR protein variation coefficient can be used for discriminating the tumors by size (<3 cm and larger), presence/absence of metastases, and evaluation of squamous-cell cancer differentiation degree. Ag-NOR protein area index and variation coefficient can be used as additional objective differential diagnostic criteria of clinical and morphological forms of squamous-cell carcinoma of the lung.

[Age changes of the connective tissue structures of human penis].

This investigation was aimed at the study of age changes of penis connective tissue structures. Tissue fragments of penis were obtained from 20 cadavers of men at the age of 20-38 years in group I, and from 20 cadavers of men at the age of 41-59 years in group II. The criteria for the exclusion of material from the research were arterial hypertension, diabetes mellitus, atherosclerosis of internal iliac arteries, Peyronie's disease, and anomalies of genital organ development. It was shown that in the cavernous body of penis, aging was associated with the increased amount and thickening of collagen and argyrophilic fibers, decreased content and thinning of elastic fibers, and the reduced amount of smooth muscle cells (SMC). The average area of fibroblast and SMC nucleolus was not different in both groups studied. The average area of endotheliocyte nucleolus was equal to 1.9+/-0.9 microm2 in group II, being lower than that one in group I, in which this index was equal to 2.1+/-0.9 microm2. No differences in the content of type III and IV collagen were found between the study groups. Age-associated decrease in the average area of endothelial cell nucleolus in the cavernous bodies may reflect the reduction of the activity of these cells and may indicate the development of endothelial dysfunction, which is one of the most important steps in the morphogenesis of age-related male erectile dysfunction.

[Topoisomerase IIalpha activity and tumor cell proliferation level from the degree of bromodeoxyuridine label in uterine body leiomyosarcoma].

The investigation was undertaken to estimate the expression of the enzyme gyrase Topoisomerase IIalpha (TOPOIIalpha) and proliferative activity from the level of bromodeoxyuridine (Brdu) in uterine body leiomyosarcoma (UBL) (n=66) versus the unchanged myometrium (UM), a tumor of uncertain malignancy potential (STUMP) (n=12), and leiomyoma (LM) (n=46). An immunohistochemical technique was used to reveal TopOIIalpha and Brdu. The findings indicated that Brdu was undetectable in UM and simple LM and that TOPOIIalpha activity was low. At the same time there was an exponential rise in the activity of the enzyme and cells during the S phase of the cell cycle from cellular LM to UBL. An increase was also noted in the study markers as sarcoma malignancy progressed. Thus, it can be said that the estimation of the number of cell S fractions and the activity of TOPOIIalpha in UM, LM, STUMP, and UBL may serve as a relatively simple and reliable method for the differential diagnosis of benign and malignant smooth muscle tumors of the uterine body and the determination of the activity of the enzyme may be used to define the degree of tumor chemoresistance in the complex treatment of patients with UBL.

[Expression of sex hormones receptors in leiomyoma with uncertain potential of malignancy and endometrial leiomyosarcoma: differentiatial diagnosis and prognostic significance].

A retrospective evaluation of progesterone (PR) and alpha-estrogen (ER) expression was carried out in 16 patients with smooth muscle tumors with uncertain potential of malignancy (STUMP) and 76 patients with uterine leiomyosarcoma (ULMS). PR expression was observed in 100% of intact myometrium and leiomyoma samples, while ER was expressed only in 37.1 +/- 4.2% and 23.5 +/- 4.1% of samples. In STUMP samples PR expression was observed in 66.7 +/- 11.7% of cases, in ULMS samples in 50.5 +/- 5.7% of cases. However, there was an inverse correlation between malignancy grade and sex hormones expression, although the number of positive cells and staining intensity didn't prove to be independent risk factors. The patients with ULMS G1 and STUMP expressing sex hormones have favorable prognosis, while negative receptor status of STUMP tumors is the marker of the worse prognosis.

[Argyrophilic nucleolar organizer region associated proteins in adenomas with varying colonic dysplasia and adenocarcinoma].

Argyrophilic nucleolar organizer region associated (Ag-NOR) proteins were studied in rectosigmoid epithelial tumors for diagnostic purposes. Silver nitrate staining was carried out in accordance with the standardized protocol. The quantity, area, area index of Ag-NOR proteins were automatically determined by computer image analysis. There were statistically significant differences in the quantity, area, area index of Ag-NOR proteins between the groups: the mucosa (lower 2/3 crypts), mild, moderate, and severe dysplasia of adenoma. Only the estimation of the area index of Ag-NOR proteins indicated statistically significant differences between severe dysplasia and highly differentiated adenocarcinoma. Colonic adenomas showed a correlation of the activity of Ag-NOR proteins with epithelial dysplasia, but no correlation with the size and histological type of their structure.

[Modification of a histochemical technique for detection of nucleolar organizer regions in histological specimens].

The authors modified the method for silver staining of argyrophilic nucleolar organizer regions (AgNORs). This modification eliminates defects of an original technique. The method accelerates the staining and prevents fallout of deposits. The modification is recommended for wide application.

[Sex hormones receptor expression and the activity of the argyrophilic proteins of the nucleolar organizer region in the intact myometrium cells and in uterine leiomyoma].

The authors have analyzed the expression of progesterone receptor (PR) and estrogen receptor alpha (ER) in comparison with the argyrophil proteins content in the nucleolar organizer region (NOR) in 106 samples of the intact myometrium and in 106 tumourous nodes of the simple leiomyoma. PR expression was shown in 100% cases of the intact myometrium and simple leiomyoma, while ER expression was far less common, 37 +/- 4.2 and 23.5 +/- 4.1%, respectively. There were much fewer AgNOR proteins in the intact myometrium than in the leiomyoma (3.1 +/- 0.5 and 5.6 +/- 0.4, respectively). Moreover, the number of AgNOR proteins was shown to depend on the presence of ER: when smooth muscle cells were ER-positive, there were fewer argyrophilic granules than when they were absent in both intact myometrium and simple leiomyoma.

[Modified method for the demonstration of argyrophilic proteins in the nucleolar organizer regions in paraffin sections].

The modified method of staining of argyrophilic nucleolar organizer regions (AgNORs) by silver nitrate is presented. This modification eliminates some disadvantages of an original technique. The method accelerates staining and prevents the precipitation of deposits.

[Association of expression of progesterone and estrogen-alpha receptors with the activity of argyrophilic proteins in nucleolar organizer regions in smooth muscle tumors of the corpus uteri].

The immunohistochemical technique was used to study the levels progesterone and estrogen-alpha receptors in the smooth muscle cells, by examining the specimens taken from 168 leiomyosarcomas (LMS) and 106 leiomyomas (LM) of the corpus uteri. The presence and degree of receptor expression were shown to be related to the proliferative activity (PA) (Ki67 protein expression), the activity of argyrophilic proteins in the nucleolar organizer region (Ag-NOR-protein) (silver-plating with AgNO3, as described by Y. Daskal) and the proteins regulating the apoptotic system (Bcl-2 expression) (93.4 +/- 1.1%). The presence of sex hormone receptors in LMS was associated with low PA (8.5 +/- 3.3%), the decreased synthesis of Ag-NOR proteins (15.1 +/- 2.7%), and high Bcl-2 activity (93.4 +/- 1.1%) although the presence of the receptors had no significant effect on p53. The negative expression of both types of receptors was characteristic for LMS and associated with high PA (19.3 +/- 3.1%), the high expression of Ag-NOR-proteins (25.3 +/- 2.6%), and a drastic reduction in the amplification of Bcl-2 (38.4 +/- 10%) in reference to the positive receptor status. Receptor coexpression was associated with relatively low PA, the expression of argyrophilic proteins and the relatively high expression Bcl-2 without any noticeable impact on the expression of p53.

[Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease].

The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD.

[Co-adaptation of enzymatic systems of cells and blood supply in smooth muscle tumors of the corpus uteri].

We investigated co-adaptation of enzymatic systems of cells using data on activity of NAD(Ph)-dependent enzymes and AgNOR proteins of vascular endothelium vis-a-vis angiogenesis in benign and malignant smooth muscle tumors of the corpus uteri. Overall metabolic activity (NAD-H2 diaphorase) was found to directly correlate with angiogenesis and endothelial vessel proliferation (r = 0.76 and 0.84, respectively). SDH-regulated oxidation in the main metabolic succession of a tricarbonic acid cycle depended on blood supply and endothelial vessel proliferation (r = 0.84 and 0.92, respectively; p = 0.04). A similar relationship was shown for anaerobic glycolysis of SDH (LDH content), on the one hand, and blood supply and endothelial vessel proliferation(r = 0.57 and 0.70, respectively; p = 0.02), on the other. Hence, metabolic profile varied in unaltered myometrium and tumor with variable cellular density and peculiar extracellular matrix. The highest levels of metabolic activity with NAD(Ph)-dependent enzyme co-adaptation was observed in sarcomas which were also characterized by the highest vascular density for endothelial proliferation.

[The morphofunctional characteristics of proteins of nucleolar organizers in uterine smooth muscle tumors].

The authors have shown the activity of argyrophylic nucleolar organizer region proteins (Ag-NOR-proteins) in the uterine leiomyomas of varying histological structure and determined their relationship to the growth rate, size, and site of a node and endometrial pathology. The investigation indicat yomas with significant sclerosis, 4.32 +/- 0.1 in simple leiomyomas, and 6.2 +/- 0.2 in cell leiomyomas (r = 0.58). In menopause, myomas with significant sclerosis and hyalinosis were characterized with a small number of Ag-NOR (1.44 +/- 0.04). Thus, the organizers numbered 12.1 +/- 0.5 and 21.7 +/- 1.0 in high- and low-grade sarcomas, respectively, which may be used in the differential diagnosis of cellular, bizarre, mitotically active leiomyomas and leiomyosarcomas.

[Ki-67 and p53 expression in gastric dysplasias and cancer].

The authors analyzed the heterogenicity of a cell population in dysplasia of varying degrees and gastric cancer from the expression of the proliferation marker Ki-67 and apoptosis activator p53 gene. Twenty-four stomachs (surgically removed for cancer) and biopsy materials (4 cases of moderate dysplasia, 4 cases of severe dysplasia) were studied. Four samples from clinically healthy individuals served as a control. The labeling index of Ki-67 in third-degree dysplasia was 37.9 +/- 2.5% and that in cancer 61.6 +/- 3.8%. There was no expression of the p53 gene in the controls. In three-degree dysplasia and cancer, the expression was 17.7 +/- 5.7% and as high as 69%, respectively. The densitometric characteristics of the labeled cells were of great diagnostic importance. Gastric cancer was represented mainly by 2 cell populations: (1) a stem cell line located in G1 with a low labeling index and a low optical density of Ki-67 and p53 and (2) an aggressive cell clone located in the S and G2 phase with marker hyperexpression.

[The microspectrophotometric criteria in estimating gastric mucosa dysplasia in non-invasive adenocarcinoma].

Computer analysis was carried out of images of changes in area and ploidy of gastric mucous nuclei associated with concomitant pathology, dysplasia and non-invasive adenocarcinoma of the stomach. In grave dysplasia, the area and ploidy of a nucleus were 213.7 +/- 3.42 microm2 and 10.2 +/- 0.2 c, and in well- or moderately differentiated cell adenocarcinoma--333.8 +/- 16.5 microm2 and 14.95 +/- 1.9 c, respectively. It is suggested that this evidence can contribute to a more accurate estimating of pathological processes taking place in the gastric mucosa when differential diagnosis between dysplasia and stomach cancer is undertaken.

[Characteristics of tumor cell nucleolar apparatus in stomach carcinoma]. / Kharakteristika iadryshkovogo apparata opukholevykh kletok pri rake zheludka.

The nucleolus in gastric carcinoma cells is changing in the course of tumor progression. The number of argentophylic granules in the nucleoli depends on tumor cell proliferative and protein-synthetic activity: rise with adenocarcinoma differentiation change from high to low degree.