[Immunohistochemical examination of MSH2, PMS2, MLH1, MSH6 compared with the analysis of microsatellite instability in colon adenocarcinoma].

Adenocarcinoma of the colon in 10-20% is associated with microsatellite instability, which can occur both in sporadic cancers and in hereditary nonpolyposis colon cancer. Our analysis of 195 cases of adenocarcinoma of the colon showed that microsatellite instability (MSI-H) was found only in 1.5% of patients. Subsequent choice of patients with suspected hereditary Lynch syndrome led to the identification of additional 17 patients with microsatellite instability. They passed an analysis of genes of repair system of unpaired nucleotides of DNA. The study showed that immunohistochemical staining of MSH2, MSH6, MLH1, PMS2 could effectively conduct a preliminary screening of the Lynch syndrome but was unable to divide cases of sporadic and hereditary MSI-H colon cancer.

[Proliferation of cancer stem cells in colorectal adenocarcinoma].

Correlation between level of ALDH1 expression and metastases development in patients with colorectal adenocarcinoma was not revealed. Proliferation of stem cancer cells (ALDH1-positive) was significantly lower comparatively ALDH-1 negative tumor cells (p < 0.001). Proliferation of stem cancer cells vary from 0,1% to 10%.

[Morphological assessment of predictive factors in adenocarcinoma of the colon].

Immunohistochemical investigation of 15 different markers in colon adenocarcinoma was carried out. Prognostic significance showed chemokine receptor CXCR4 and Ki-67. Predictive significance was revealed for thymidylate synthase (TS) and thymidine phosphorylase (TP).

[Carcinosarcomas of the uterus: molecular-genetic and morphological features].

13 cases of uterine carcinosarcomas have been studied by molecular-genetic method. The impairment of some genes (K-RAS gene in the first exon, TP53 in the 5th-9th exons, PTEN in the 5th and 8th exons) has been found out. The loss of heterozygosity of TP53 gene in epithelium and mesenchyme of the uterus has been detected. According to the estimation of impairment the studied tumors was divided into monoclonal and biclonal ones. This stratification could be use as prognostic criteria of uterine carcinosarcomas clinical presentation.

[Carcinosarcoma of the corpus uteri: potential of p53, PTEN and COX-2 expression for survival].

Clinico-morphological and immunohistochemical examinations were carried out in 46 patients with carcinocarcinoma of the corpus uteri to evaluate p53, PTEN and cyclooxygenase-2 (COX-2) expression in mesenchymal and epithelial cells of tumor. p53 expression in the epithelium and that of COX-2 in both compartments appeared to be unfavorable prognosticators of survival while that of PTEN is a lesser one in significance.

[Positron emission tomography with 18F-FDG compared with proliferative activity of tumor cells in different subtypes of non-Hodgkin lymphoma].

In the course of this study we determined the ability of positron emission tomography (PET) with the 18F-FDG to detect non-hodgkin lymphoma lesions, assess their proliferative activity and differentiate aggressive tumors from indolent. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV). It was compared with tumor grade and proliferation fraction determined by Ki-67 staining. In patients with indolent lymphoma, mean SUV was 2.5 +/- 0.6. In patients with aggressive lymphoma a significantly higher 18F-FDG uptake was observed (mean SUV was 8.1 +/- 1.3). Linear regression analysis indicated significant correlation of 18F-FDG uptake to biopsy samples proliferation fraction in patients with diffuse large B-cell lymphoma (r = 0.55, p = 0.05) and indolent non-Hodgkin's lymphoma (r = 0.7, p < 0.05). In this clinical study 18F-FDG uptake correlates with the aggressiveness of malignant lymphomas and with biopsy samples proliferative activity.

[New prognostic factors in the treatment of patients with stage-III Hodgkin's disease].

Our data are presented on evaluation of chemoradiotherapy of 365 patients with stage III Hodgkin's disease. Patients with stage IIIA tumors revealed the following significant differences of overall and relapse-free survival (p < or = 0.00001): 15-year overall survival (nodular sclerosis G1) - 95% vs.G2 - 45%; 15-year relapse-free survival: G1 - 86%, G2 - 32%. In stage IIIB group, overall survival (50%) was significantly lower as compared with 70%. Involvement foci significantly regressed by less than 75% (p = 0.044) after 2-4 cycles of preliminary combination chemotherapy. Our results suggest that differentiated criteria be used for prognosis of stage III Hodgkin's disease treatment.

[The place of dendritic cells in the microenviroment in Hodgkin's lymphoma].

Dendritic cells (DCs) are the least studied microenvironment elements in Hodgkin's lymphoma (HL). Ninety-five lymph nodes were morphologically and immunohistochemically studied in patients with classical HL. The authors found CDla- and langerin-positive DCs in the presence of T lymphocytes, which were localized in the close proximity to neoplastic Reed-Sternberg cells (RSCs). There were also CD23-positive follicular DCs, which were typically located at the periphery of tumor foci, in the areas of residual follicular structures, were surrounded by B lymphocytes and were rarely associated with RSCs. There were two morphologically distinct groups among the CD 1a- and langerin-positive DCs; one had developed cytoplasmic processes, which formed a network around the RSCs (probably a more mature/functionally active form); the other had round cells with short cytoplasmic processes, loosely distributed around the neoplastic cells (a less mature/active form). The function and role of CD1a- and langerin-positive DCs in HL call for further investigation. The topographic closeness of these DCs to RSCs suggests that these cells play a considerable role in the pathogenesis of HL.

[Expression of contractile proteins alpha-actin and myosin of smooth muscle cells and collagen of IV type in human placenta at placental insufficiency in III trimester of pregnancy].

Changes of expression of contractile proteins (alpha-actin and myosin of smooth muscle cell) and of collagen of IV type in stroma of human placental villi were studied at the diagnosed placental insufficiency (PI) in III trimester of pregnancy. The study revealed pronounced disturbances of expression of contractile proteins and collagen of IV type at PI. It is shown that in perivascular envelopes of vessels of stem and intermediate villi there is present a much greater amount of cells expressing smooth muscle actin and myosin. These cells are arranged by the denser concentric layers and more compactly than in norm and fill the intervascular space inside the villi. The width of perivascular envelopes of vessels is higher, while vascular lumens are lower than in norm. In terminal villi the capillary walls are thickened and the number of pericytes immunopositive against the smooth muscle cell alpha-actin and myosin as well as collagen of IV type is increased. The change of synthesis of the cytoskeletal contractile proteins and collagen of IV type is shown to lead to structural disturbances of villi of different types and of perivascular areas and vessels, which doubtlessly indicates their participation in pathogenesis of placental dysfunction and of disturbance of placental hemodynamics.

[Structural changes in human placenta and its vascular bed in syndrome of placentar failure].

Study of born placentas with chronic functional failure established in the III pregnancy trimester has revealed several characteristic structural alterations of placentar villi and of its vascular bed elements. There has been shown a decrease of the number of terminal villi and an increase of their sizes (approximately 3 times) as compared with norm, a change of transformation of cytotrophoblast into syncytiotrophoblast, thickening of vascular endothelium, a decrease of the number of capillaries-sinusoids, and a decrease of the number of syncytiocapillary membranes, which leads to deterioration of conditions of the maternal-fetal diffuse exchange. It has been established that in placentar failure, expression of the vascular endothelial growth factor (VEGF) by cytotrophoblast cells, syncytiotrophoblast, and Kashchenko-Hoffbauer cells is enhanced as compared with norm, which can be considered a reaction to a decrease of intensity of placentar blood circulation.

[Kinetic features of ascites and solid Ehrlich tumors].

Such biological parameters as tumor volume, Ki-67 and p53, which characterize the development of ascites and solid tumor of Ehrlich were evaluated. The kinetic curve of growth of ascites tumor was S-shaped (Gomperts) while that of the solid one--cubic (Speer-Retsky). Ki-67 expression level was found to be in cyclic correlation with duration (3 and 6 day intervals) which might be worth considering when working out therapeutic procedure. Moreover, no increase in cell death was observed when tumor growth slowed down.

[Diabetes mellitus and obesity: projection onto oncological morbidity].

Peculiar features of human morbidity and their changes in time are registered chronologically starting from the XVII-VYIIIth centuries. After the period of predominantly infectious diseases, chronic and non-communicable conditions continued to gain momentum in the last 3-5 decades. Side by side with AIDS, accidents, effects of smoking etc, the global epidemics of diabetes mellitus and obesity comes up to take a leading place in the general population morbidity. In this communication, possible causes of this situation and its possible association with cancer are considered based on the results of original studies. Measures for the prevention and treatment of these diseases are discussed.

[Analysis of polymorphisms in genes of insulin receptor substrate-1 and enzymes involved in estrogen biosynthesis and metabolism among breast cancer patients with BRCA1 mutations].

Polymorphisms in genes involved in steroidogenesis as well as sensitivity to insulin as potential cancer risk factors have received constantly-growing attention over this decade. The peculiarities of endocrine and metabolic features of cancer identified earlier in BRCA1 mutation carriers prompted an investigation of the frequency of polymorphisms in the genes of IRS-1 and enzymes of estrogen biosynthesis and metabolism, such as aromatase (CYP19), estrogen 4-hydroxylase and catechol-O-methyl transferase (COMT) in 12 BRCA1 mutation carriers and in 22 non-carriers. The results were compared with the earlier data from the patients with the same diagnosis (n = 110 and n = 295, respectively) but untested for BRCA1 mutation. BRCA1 mutation carriers tended to show increasing fractions of heterozygotes for AG (COMT Vall58Met p = 0.24) and active allele A6 featuring 11 TTTA repeats in the 4-th introne [corrected] of CYP19 gene (p 0.09). [corrected] The frequency of co-occurring CC (CYP1B1) Arg48Gly), AG (COMT Vall58Met ) and A6 (CYP19) in BRCA1 mutation carriers (5 out of 12, 41.6% ) was significantly higher than that in non-carriers (2 out of 22, 9.1% ) (p = 0.03). Immunohistochemical assay showed aromatase expression levels to be the highest among cases of BRCA1 mutation and A6 (CYP19) while CYP1B1 expression was the highest in those of combination of BRCA1 mutation and low-activity AA genotype (COMT Vall58Mer). Our results warrant further large-scale cooperative studies of the problem.

[Some kinetic characteristics of cervical cancer].

Proliferation parameters such as mitotic index, tumor growth rate and cell loss were identified in 1,048 squamous cervical carcinoma patients treated at the Center's Clinic (1951-1996). Mitotic indices ranged 0.2-5.1% (average 1.13 +/- 0.03%), Ki-67--4.1-97.8% (average 49.97 +/- 3.02%). A direct and significant correlation between the two latter parameters was established. Cell loss levels ranged 59-99.9% (average 97.2 +/- 0.002%). Our results suggest that the correlation between tumor growth rate and cell loss might be of the utmost importance among the other prognostic factors.

[An immunohistochemical study of aromatase, estrogen 4-hydroxylase and fatty acid synthetase in breast cancer tissues from BRCA1 mutation carriers].

Breast cancer in germline BRCA1 mutation carriers features a peculiar endocrine and metabolic profile which is yet to be studied properly in clinical settings. We used a novel immunohistochemical method to compare expression levels of aromatase, estrogen 4-hydroxylase (CYP1B1) and fatty acid synthetase in breast cancer tissues from 12 BRCA1 mutation carriers and 22 non-carriers. Rates of aromatase in carriers were significantly higher than in control (p=0.04) to match the data obtained earlier in cell lines employed in down-regulation of the wild BRCA1 gene. These findings make a case for use of aromatase inhibitors in such patients. No differences in CYP1B1 and fatty acid synthetase expression levels were found between the mutation and the wild BRCA1 gene groups. Further search is warranted for manifestations of excess genotoxic effects of estrogens and enhanced lipogenesis in BRCA1 mutation carriers.

[The Saint Petersburg Society of Pathologists is 100 years old].

The paper describes the history of the Saint Petersburg Society of pathologists since it was founded in 1909. It shows what great role is played by outstanding Russian medical scientists who have established their own schools of pathomorphologists and are respected in our and foreign countries. The activities of the society's members in research developments in cardiovascular and infectious diseases, cancer morphology, etc., as well as their practical participation in the work of the health care facilities of the city and its region are characterized. This work is characterized by the permanent conformance to the world standards of human pathology as a basic science of the present day, by steadily maintaining the established traditions of the Saint Petersburg school. The authors follow the evolution of a pathologist and his/her becoming to a clinical pathologist as the problems facing pathomorphology are extended and its methodic and methodological capacities are improved.

[The proliferative properties and regulators of the mitotic cell cycle of prostate adenocarcinoma].

The authors have made an immunohistochemical determination of Ki-67, topoisomerase IIalpha, cyclins D1, A, and B1, and calculated their indices in 145 acinar adenocarcinomas of the prostate. This tumor is characterized by a wide range of Ki-67 index (from 3 to 90% or more) although 90% of cases are in the range of 5-35%. Other study proliferative markers are distributed in the following descending order: cyclin D1 (1.32 to 63.27%), topoisomerase IIalpha (0.47 to 53.17%), cyclin A (0.46 to 28.09%), and cyclin B1 (0.29 to 9.34%). The indices of the study markers are increased as the Gleason grade is higher. The exception is cyclin D1 that shows high expression in intact and tumor tissues, which is frequently greater than that of Ki-67, and its stable expression independent of the Gleason score.

[Investigation of biological features of uterine carcinosarcoma].

Results of clinico-morphological and immunohistochemical studies of 44 cases of carcinosarcoma of the uterus are presented in an attempt to provide pathogenetic rationale for prognosticators of the disease. Immunohistochemical reactions were used to evaluate the expression of genes and mediators p53 and PTEN and cyclooxigenase (COX-2) in cells of mesenchyme and epithelium of tumor to gauge the influence of either component on its biological behavior. All patients were divided into two groups depending on whether they revealed expression of p53, PTEN and cyclooxigenase or not. The end results--overall survival and complete remission duration--were compared in both groups. No dominance of either component of carcinosarcoma was established.

[The significance of immunohistochemistry in the investigation of liver neoplasms: differential diagnosis, prognostic markers].

The immunohistochemical investigation used 55 primary hepatic tumors (hepatocellular carcinoma (HCC)--32, cholangiocellular carcinoma (CCC)--23). Wide panels of such antibodies as hepatocytic marker (Hep Par--1) CK-8, CK-19, polyclonal CEA, CD10, alpha-fetoprotein, TTF-1 as well as proliferative features of HCC (Ki-67) including regulators of stage-to-stage transition through mitoses of tumor cells (cyclin-D1 and A, genes p53 and RB), unrestricted tumor cell mitosis (telomerases), and intercellular adhesion marker (beta-catenin) were employed for differential diagnosis of neoplasia. The most efficient marker HCC was Hep Par--l (sensitivity--100%, specificity--92%) while the sensitivity of CCC (CK-19) was 83% and specificity--78%. Of particular importance for differentiation between HCC and CCC were the nature of microcirculatory flow identifiable with the aid of CD31 and presence of pseudocapsule in HCC detected by means of calponin. CEA and CD10 played a part too while the remaining markers were either expressed very seldom (alpha-fetoprotein) or absent (TTF-1). Most nuclear antigens (Ki-67, cyclin-A, p53 and RB) were intensely expressed in poorly-differentiated HCC cells. Cyclin-D1 and mutated suppressor-gene p53 expression involved lowered overall and relapse-free survival.