The earliest (in preclinical stages) detection of malignant tumor process is a key factor in successful treatment of cancer. What methods and approaches are most suitable for this purpose? The paper presents current understanding of the biological basis of the process of malignancy and analyzes the comparative opportunities and prospects for early detection of cancer using molecular genetics and immunochemical approaches.

Molecular genetic analysis of lung tumors is often essential for the proper choice of therapy. EGFR mutation is a well-known marker of sensitivity to gefitinib, erlotinib and afatinib; ALK-translocations make tumor sensitive to several ALK inhibitors; low intratumoral expression of DNA repair genes (ERCC1, BRCA1, etc.) may increase the therapeutic index of platinum-based drugs. Usually these markers are evaluated using formalin-fixed paraffin-embedded tumor tissues. The goal of this work was to assess utility of archived cytological lung cancer specimens as an alternative source of material for molecular genetic testing. We analyzed paired histological and cytological lung adenocarcinoma specimens. Comparison of results within the pairs showed that cytological material can be used instead of histological material for qualitative analyses (detection of EGFR mutations or ALK-translocations); however, gene expression measurements, obtained by quantitative real-time PCR, may differ significantly in histological and cytological samples from the same patient.

In this study, for the first time the expression of β₂ and β₄ isoforms of RARβ gene was investigated in group of 19 patients with the newly diagnosed multiple myeloma. The expression of both RARβ₂ and RARβ₄ isoforms was detected in all patients, but it was different and had opposite tendency. We showed that RARβ₄ expression level positively correlated with VEGF-A and VEGFR1 expression levels. It was found that higher levels of RARβ₄/VEGF-A/VEGFR1 co-expression were defined of patients with statistically significant increase of plasma cell level and paraprotein concentration. The median overall survival was lower in patients with RARβ₄, over-expression, while the maximal median overall survival was observed of patients with RARβ₂ down-regulation and nearly absolute RARβ₄inactivation.

There were examined 219 women of Kyrgyz nationality (mean age 51 ± 9.7 years). 117 female with breast cancer (BC) and 102 apparently health controls. The diagnosis of breast cancer was confirmed histologically. DNA was prepared from whole blood samples. XRCC1 genotypes Arg399Gln were examined using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP). The frequency of the variant 399Gln allele and heterozygous genotype Arg399Gln of the Arg399Gln polymorphism of the XRCC1 gene were significantly higher among women with breast cancer compared with control subjects (p < 0.05). The Arg399Gln polymorphism of the XRCC1 gene is associated with breast cancer risk in a Kyrgyz women when using additive model (χ² = 4,901; p = 0.0268) general model (χ² = 13,86; p = 0.0010) and dominant model of inheritance (χ² = 11.18; p = 0.0008). Women having the 399Gln allele had 1,57 fold (95% CI 1.7-2.30; p = 0.002) higher risk of developing BC compared with subjects carrying neither of these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2.77 fold (95% CI 1.6-4, p = 0.002) higher risk of BC. Thus, the heterozygous genotype Arg399Gln and 399Gln allele of XRCClgene are associated with an increased risk of breast cancer in Kyrgyz females.

Skin melanoma is an etiologically heterogeneous disease, the development of which is related to a complex interaction of environmental factors and individual genetic characteristics. This article provides current molecular-genetic aspects of familial cases of melanoma and polymorphism of genes directly related to the risk of developing this hereditary disease. The studies of hereditary cancer cases add our knowledge of mechanisms oncotransformation, genetic changes in signaling pathways, which are responsible for invasiveness, metastasis and drug resistance of melanoma cells of the skin.

Studies carried out on samples of tumor and non-tumor tissue indicate that markers of radiosensitivity for predicting individual patient response to the planned radiation therapy may be the indicators of apoptosis and molecular profiles read from the DNA of patients. At present there is developed a technology for rapid and economical determining of indicators for the reasonable use of radiation therapy in the radiological practice in patients with breast cancer, bladder cancer and malignant glioblastomas by means of an evaluation of radiosensitivity of the DNA of blood.

The present study is dedicated to the search of human glioma "cells of origin". Specimens of the tumor tissue have been analyzed via the RT-PCR method to potentially reveal the expression of molecular markers characteristic of various cells of nerve tissue (NeuN, MOG, MBP, NG2, Olig2, Vimentin, GFAP, AldhlL1), as well as markers of stem (Oct4, c-Kit) and cancerous stem (CD133) cells. We have shown that the expression profiles of these markers for different types of gliomas intersect, which does not allow to determine the type of "cells of origin". So, in order to study the origin of glioma using cell lines derived from primary cultures, we need a more sophisticated culture conditions, rather than the commonly used serum-based media.

P53 protein is considered to be the major tumor suppressor in human cells. Cancer cells do not survive if the p53-mediated signaling pathways function properly. However, about half of all malignancies still express wild type p53. One of the explanations to this is that p53 is suppressed by overexpression of p53-specific E3-ubiquitin ligases: Mdm2, MdmX, Pirh2 and Cop1. Pharmacological inhibition of protein-protein interactions between p53 and these negative regulators is a promising therapeutic approach to treat cancers retaining wild type p53. To date, a series of chemical inhibitors of p53 interactions with Mdm2 and MdmX E3-ubiquitin ligases have been discovered and characterized. Several of them are in the early stages of clinical trials. Despite this fact, their clinical efficacy may be hampered by a number of reasons, including tumor-specific expression of multiple isoforms of the target E3-ligases, which become inert to treatment with small molecules. This and other biochemical mechanisms of possible resistance of tumor cells with wild type p53 to small molecules against its negative regulators will be discussed in this review.

Type 1 multiple endocrine neoplasia syndrome (MEN-1) is a rare autosomal dominant disorder caused by mutation in the MEN-1 gene and manifest as a combination of tumours of parathyroid glands, endocrine pancreas, and adenohypophysis. Familial isolated hyperparathyroidism (FIHP) is another rare autosomal dominant disorder characterized by the development ofparathyroid tumours as the sole endocrinopathy within a single family. The notion of FIHP encompasses different hereditary forms of primary hyperparathyroidism, such as a variant of MEN-1 syndrome. This paper is a brief literature review of the problems related to primary hyperparathyroidism, MEN-1, and FIHP. Also, It describes a family presenting with genetically confirmed MEN-1 syndrome, manifest as primary hyperparathyroidism.

Despite the long-term history of HER2 testing in breast cancer (BC), the results of its study are frequently interpreted ambiguously. The introduction of the new 2013 ASCO/CAP guidelines is aimed to further optimize HERS testing in view of new scientific evidence for the biological characteristics of BC.

to estimate the diagnostic and prognostic value of analyzing the abnormal overexpression of the chimeric protein ERG, encoded by the chimeric gene TMPRSS2/ERG, in prostatic neoplasias.

to investigate the specific features of the expression of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloptoteinase 2 (TIMP-2), urokinase-type plasminogen activator (uPA), and angiotensin-converting enzyme (ACE) in cervical squamous cell carcinoma (CSCC).

to estimate the predictive and prognostic factors using morphological studies in patients with colon cancer to increase survival rates.

The paper describes an anatomical pathology case of synchronous multiple primary carcinoma in a 75-year-old man with a tumor-to-tumor phenomenon of small cell lung carcinoma metastasis to clear cell renal cell carcinoma (tumor-to-tumor).

To analyze 60 cases of solid pseudopapillary tumors (SPTs) of the pancreas, to reveal their most characteristic clinical and morphological features, and to study their possible histogenesis.

To estimate the frequency of BRAF V600E mutation in melanoma patients and to assess an association of this type of mutation with the clinical and morphological characteristics of the disease.

To determine the genetic forms of follicular cell thyroid carcinoma (FCTC) (papillary and follicular thyroid carcinoma (PTC and FTC)), to identify criteria to individually predict the development of the same disease for relatives, and to assess the role of molecular markers in the diagnosis, prognosis, and treatment of this disease.

To determine the predictive and prognostic value of koilocytosis, expression of E6 HPV types 16/18, p16INK4a, p53 in patients with locally advanced HPV-associated squamous cell carcinoma of oral cavity and oropharynx. In biopsy specimens of squamous cell carcinomas of oral cavity and oropharynx from 60 patients performed koylocytes count, immunohistochemical detection of HPV 16/18 types E6 protein, proteins p16INK4a and p53. Koilocytosis was detected in 50 patients (83.3%); in all 60 patients (100%) were simultaneous expression of p16INK4a and E6 HPV types 16/18; p53 expression was found in 37 patients (61.7%). After combined treatment (induction chemotherapy followed by radiotherapy) stable disease (SD) was detected in 11 patients (18.3%), partial response (PR) - in 25 patients (41.7%), complete response (CR) - in 24 patients (40.0%). There were no cases of disease progression. Treatment effect correlated with expression of p16INK4a (ρ = 0.3, p = 0.024) and expression of p53 (ρ = - 0.3, p = 0.019). Patients with a low expression of p16INK4a (2 points) and high expression of p53 (4 "+") had a high level of SD and had no CR. For all patients, the median of overall survival (OS) was 17 months, 1-year cumulative survival rate was 66.7%, 2-year cumulative survival rate - 35.0%. Median of overall survival was correlated with koilocytosis (ρ=0.5, p<0,001) and expression of E6 HPV types 16/18 (ρ=0.9, p<0.001), p16INK4a (ρ=0.9, p=0.037), p53 (ρ=-0.9; p<0.001). Patients with low expression of p53 (0 and 1 "+") had cumulative 1-year survival rates 87% and 90%, respectively (p<0.001), 2-year survival rates - 52% and 80%, respectively (p=0.015). In the Cox proportional hazards model the significant prognostic factors were prevalence of primary tumor (OR 2.2, 95% CI 1.3 - 3.5, p=0.003) and p53 expression (OR 1.3, 95% CI 1.1=1.7, p=0.016). High expression of p16INK4a associated with a high effect of combined treatment, high expression of a p53 - with low effect of treatment. Koilocytosis and expression of E6 HPV 16/18 types have no predictive value. Median of overall survival correlated with koilocytosis, expression of E6 HPV types 16/18 and p16INK4a. P53 expression is an independent predictor of negative prognosis for overall survival. Increase in the level of p53 expression is associated with a reduction in overall survival and cumulative 1- and 2-year survival rate. For patients with low expression of p16INK4a or high p53 expression, surgery is advisable to consider as first stage of treatment.

Two glioblastoma groups, which are distinguished from each other by expression level of 416 genes (P < 0.05), were determined using a mathematical model of linear Boolean programming on the basis of gene expression data, obtained by microarray analysis of the glioblastomas and available in Gene Expression Omnibus (GEO) data base. The expression level of 15 genes was more than two-fold higher in the first group of glioblastoma (80 samples) in comparison with the second group (144 samples) and 401 genes and--more than two-fold lower as compared to the second group. 10 of 15 genes, which expression level prevailed in the first group, encode the proteins involved in cell cycle regulation and cell proliferation. A significant percentage of 401 genes are the genes that encode proteins involved in the functioning of neural cells and participating in the processes such as synaptic transmission, neurogenesis, the formation of myelin sheath, axon formation. Kohonen map, built on the basis of the data of 15 genes with prevailed expression in the first group and 60 (of4 01) genes, whose expression level elevated in the second group, confirmed the existence of two glioblastoma groups with specific gene expression profiles. Distribution of the glioblastomas into two groups may reflect two pathways of astrocytic glioma development, one of which leads to the formation of tumors with higher levels of gene expression, which protein products are involved in cell cycle regulation and proliferation. On the other hand, the existence of two molecular variants may reflect different states of glioblastoma progression.

The expression of the Igf-1 gene in mice liver at different stages of development of hepatocellular carcinoma induced by diethylnitrozamine--from the initial diffuse tissue dysplasia and nodular hyperplasia to the development of multiple adenomas and carcinoma--has been analyzed. It was marked that the level of Igf-1 expression in all liver neoplasms decreased; it increased only in the liver tissue surrounding the carcinoma. The dependence of Igf-1 expression on inflammatory processes accompanying tumor growth was analyzed on the model of acute liver damage by diethylnitrozamine. It was established that the level of Igf-1 expression in liver tissue under acute damage in sexually mature mice was the same as in the control group. By the means of semiquantitative evaluation of the products of two Igf-1 splice isoforms--locally active (Mgf) and circulating (Igf- 1v4)--it has been shown that the amount of mRNA of both isoforms in hepatocellular carcinoma was lower, and in tissue surrounding the tumor higher, than in the samples of the control group. At the same time, the proportion of transcripts of isoforms was stable.