Background: Pathological complete response is a predictor of favorable clinical outcome in patients with tripl-negative breast cancer. Over the last years there was an increasing interest to the search for predictive markers of tumor response to neoadjuvant chemotherapy (NACH). The purpose of the study is to assess predictive markers: cytokeratin 5/6, epidermal growth factor receptor (EGF1) and proliferation marker Ki-67 in patients with basal-like tripl-negative breast cancer.

Materials and methods: The study included 44 patients with basal-like tripl-negative breast cancer, who received 2–4 courses of NACH with FAC and CAX regimens. Estrogen and progesterone receptors, Her-2/neu, the levels of proliferative activity of Ki-67, CK 5/6 and EGFR1 were determined in all breast cancer biopsies. Response to NACH was assessed using RECIST scale.

Results. Pathological complete response was observed in 69 % of breast cancer patients, who had only EGFR1expression in tumor tissue (р=0.01). The best response was noted at high proliferative activity of tumor cells (90 %, р=0.0006) and when using CAX regimen (81 %, р=0.004). The model of logistic regression enables prediction of pathological complete response with high rates of sensitivity (82 %) and specificity (67 %).

Conclusion. The results obtained indicate that the studied markers can be used as predictors of clinical outcome and the devised model of logistic regression can be used to predict the chemotherapy response of breast cancer based on clinical pathological variables.

Introduction. Up to 30 % of patients with non-small cell lung cancer have locally advanced tumor. Increased waiting time for radiation therapy and/or chemotherapy can result in tumor progression and impaired survival.

The purpose of the study was to evaluate the influence of the length of time before starting therapy on the overall survival in patients with inoperable locally advanced non-small cell lung cancer.

Materials and methods. In the retrospective study, 139 patients with non-small cell lung cancer, receiving chemoradiotherapy were divided into subgroups by the length of time before starting therapy. The overall survival was assessed using the Kaplan-Meier method with determination of differences between groups by long-rank test, and the cumulative overall survival was compared using the χ2 test. The Cox regression model was applied to evaluate the effect of covariates on overall survival.

Results. Chemoradiotherapy was started within 1 month after diagnosis in 87 (63 %) patients and in 31 days and later in 52 (37 %) patients. Distribution by initial prognostic factors was uniform, except for exploratory thoracotomy, which was performed more often in patients who received chemotherapy within 1 month after diagnosis (р=0.001). The median overall survival rate was 14.2 months (95 % CI: 11.8–16.7) for patients who received chemoradiotherapy within 1 month after diagnosis and 19.1 months (95 % CI: 14.7–23.5) for patients, who received therapy at least 1 months after diagnosis (χ2 =0.562, р=0.453). Risk ratio (RR) of death was 0.87 (95 % CI: 0.59–1.26) in patients with late onset of special treatment.

Conclusion. The retrospective analysis showed that time before onset of chemoradiotherapy in patients with stage III non-small cell lung cancer had no influence on prognosis of survival, with the initial chemotherapy as well as radiotherapy. These results require confirmation in randomized trials.

This study presents the new evidences for DNA Copy Number Aberration (CNA) within breast tumors and its association with the efficacy of preoperative (neoadjuvant) chemotherapy.

Methods. 68 breast cancer patients were treated with 2–4 courses of neoadjuvant chemotherapy. Unbalanced chromosome abnormalities – numeric and structural CNA in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). Immediate tumor response to NAC was measured in accordance with recommendations of WHO.

Results. 1q43 amplification correlated with good response to NAC. Partial tumor regression was observed in 83 % (33/39) of patients with 1q43 amplification, whereas no response to NAC was found in 78 % (18/23) of patients with normal 1q43 region (р=0.00085 Fisher test, Bonferroni correction). Among patients with chromosomal deletions at 11q22.1-23.3, 83 % (25/30) manifested the response to NAC, whereas 68 % (23/34) deletion-free persons did not respond to therapy. Combination of amplification and deletion markers increased the sensitivity and specificity for predicting response to NАС. Amplification in 1q43 along with deletion in 18р11.21 loci resulted in partial tumor regression in 92 % (35/38) of patients. In the case of the normal status of these loci, 81 % (21/26) of patients had no response to NAC (р=0.000002).

Conclusion. The presence of unbalanced, chromosome abnormalities in 1q, 11q и 18p loci within breast tumors before treatment correlates with good response to NAC and can be used as a marker for predicting response to neoadjuvant chemotherapy with high confidence interval.

Small non-coding RNAs (miRNAs) are not only an important regulator of gene expression by participating in almost all basic processes in the cell, but are specific molecules and can be used for many applications in clinical diagnostics. In our study, we assessed the level of miRNA expression in tumor tissue of patients with head and neck tumors of various sites. New data regarding the expression pattern of eight miRNAs in tumor tissue from patients with cancer of the larynx, tongue and papillary thyroid carcinoma, namely: miR-18a, -21, -155, -200a, -200c, -205, -221 and -494 were obtained. The spectrum of miRNA-specific localizations was analyzed, suggesting the existence of differences in the mechanisms of participation of the same miRNA in carcinogenesis of tumors of different epitopes of the head and neck. The panel of miR-200a, -200c, -21 and -205 was shown to be specific for determining the two locations (laryngeal and thyroid cancers) and probably can be used to define the site of a secondary tumor and / or metastasis of unknown origin.

Pathomorphology study of bone marrow fibrosis in patients with multiple myeloma by using morphometric image analysis software was performed. It was revealed that bone marrow fibrosis occurs 1.5 times more frequently in relapse of disease than in the initial presentation of the disease and in response to chemotherapy. The highest relative area of fibrous tissue in marrow fibrosis of 2nd and 3rd grade is observed in relapsed multiple myeloma. There is a direct correlation between the relative area of the tumor tissue in the bone marrow and the relative area of fibrous tissue in bone marrow fibrosis of the 1st and the 2nd grade. Chemotherapy is a factor associated with bone marrow fibrosis of the 2nd and the 3rd grade. Gender and age of the patients are not associated with marrow fibrosis.

Hormone therapy with tamoxifen is the commonly used treatment for luminal breast cancer. However, it appears to be ineffective in 20–40 % of cases and the possible reasons of this failure are related to the features of distribution and structure of estrogen receptor alpha (ERα) in tumor tissue. Realization of the therapeutic effect of tamoxifen is carried out by blocking the activation center of AF-2 receptor. The change in the functional state of this receptor resulted from single-nucleotide polymorphisms coding 2228480 (G/A) in exon 8 of ERα gene is considered as a possible cause of treatment failure with tamoxifen.

The purpose of the study was to analyze the relationship between the ERα expression and polymorphic variants in exon 8 of the ERα gene and the efficacy of tamoxifen in patientswith luminal breast cancer.

Material and methods: The study included 97 patients with stage T1–2N0–1M0 luminal breast cancer, who received adjuvant chemotherapy with tamoxifen. The follow-up ranged from 24 to 130 months. Long-term treatment outcomes were assessed upon the progression of the disease with the evidence of distant metastases. In tumor tissue samples, the ERα expression was studied using the immunohistochemical method. The values of the ERα expression intensity as well as the character of ERα distribution were assessed. Polymorphic variants of exon 8 of the ERα gene were studied using real-time PCR.

Results. The heterogeneous distribution of ERα gene was observed in 86.5 % cases with diseases progression and in 58.3 % of cases with favorable disease outcome (р=0.0072; χ2 =7.22). Mutation of rs2228480 (G/A) in exon 8 of the ERα gene was observed in 19.4 % of cases. Mutations were not noted in tumor cells with homogenous distribution of the ERα gene and mutations were found in 25.7 % (р=0.014; χ2 =6.09) in heterogeneous distribution. Mutation in exon 8 of the ERα gene was shown to occur more often in patients with disease progression (р=0.01; χ2 =6.52).

Conclusion: The character of the ERα gene distribution and the presence of mutation in exon 8 of the ERα gene in tumor tissue can be considered as additional predictive factors of response to therapy with tamoxifen in patients with luminal breast cancer.

The expression of matrix metalloproteinase (MMP) genes and activity of proteasomes and calpains were studied in patients with precancerous laryngeal lesions and laryngeal cancer. A significant increase in MMP-1 and MMp-14 gene expression was shown in laryngeal cancer tissue compared to that observed in dysplastic laryngeal tissue. Furthermore, the activity of proteasomes and calpains was significantly higher in laryngeal cancer tissue than in dysplastic laryngeal tissue. The results obtained indicate that extracellular and intracellular proteases play an important role in the development of laryngeal cancer. The detected features of pathogenesis of laryngeal dysplasia and laryngeal cancer will allow the additional objective criteria for predicting the risk for malignancy to be identified.

The purpose of the study was to evaluate the nosological structure of central nervous system (CNS) tumors and the role of immunohistochemical assay in verification of their histogenesis.

Material and methods. 162 biopsy and surgical specimens of CNS tumors obtained from neurosurgical departments of hospitals in Novosibirsk and Siberian Federal District in the period 2004–2013 were studied.

Results. In the structure of primary CNS tumors, astrocytic tumors were the most common (47.9 %) followed by meningeal tumors (9.3 %), and oligodendroglial tumors (6.3 %) located predominantly in in the cerebral hemispheres of the brain (81 %). CNS metastases occurred on 11% of cases, there were mainly malignant epithelial tumor metastases. Inflammatory pseudotumors were observed in 3.1 % of cases. The use of immunohistochemistry with a broad panel of antibodies, mainly: pan-cytokeratin, vimentin, leukocyte common antigen, epithelial membrane antigen, glial fibrillary acidic protein allowed the histogenesis of CNS tumors to be clarified in 29.6 % of cases.

Molecular nuclear medicine plays an important role in the diagnosis and therapy of cancer. Radioimmunodetection and radioimmunotherapy (RIT) involve the use of antibodies conjugated with diagnostic or therapeutic radionuclides, respectively. More often for RIT use the monoclonal antibodies against tumor-associated antigens, radiolabeled with alpha or beta-emitters. Encouraging results have been achieved with this technology in the management of hematologic malignancies. On the contrary, solid tumors have been less responsive. Radioimmunotherapy therefore is considered more suitable for the treatment of microscopic or minimal residual disease, allowing radiolabeled monoclonal antibodies to achieve uptake in tumors high enough to result in tumoricidal radiation doses. Despite these encouraging results, new potential target for radioimmunodetection and RIT should be found. For this purpose, a series of experiments will be performing to investigate the biodistribution and the therapeutic efficacy of radiolabeled monoclonal antibodies in cell culture and animal models.

The role of high-field magnetic resonance imaging in diagnosis and assessment of invasion and local spread of bladder cancer has been presented.

We obtained a new monoclonal antibody (mAb) against tumor-associated protein PMEPA1 (Prostate Transmembrane Protein, Androgen Induced 1) for which is shown differential expression in some tumors. To test the specificity of obtained mAb we have produced a full-length recombinant PMEPA1 in transfected HEK293T cell line. After transfection of the plasmid vector pIRES-EGFP, containing the insertion coding PMEPA1 gene we evaluated PMEPA1 protein expression in HEK293T cells lines by immunocytochemical study and western-blot analysis. Ability of the new mAb binds PMEPA1 in clinical specimens is shown by immunohistochemistry on histological sections of prostate tissue used as positive control. New antibody may provide a basis for development of commercial antibody test for evaluation of protein expression in human biological samples.

Mixed pleural mesothelioma is uncommon spontaneous tumor in laboratory mice. The case of this tumor in BALB/c mouse has been described in the paper. It is essential that myocardial metastasis has been observed. Differential diagnostics between pleural mesothelioma, pleural dissemination of bronchoalveolar adenocarcinoma and malignant thymoma has been discussed in relation to described tumor.

Cervical cancer is the most common malignancy associated with pregnancy. The clinical case presented in this paper is of interest for several reasons. First, human chorionic trophoblast was shown to be a target for HPV, resulting in termination of pregnancy, as evidenced by the analysis of HPV of the abortion material (high HPV 16 viral load). In addition, iliac lymph node metastasis occurred in minimal tumor invasion, significantly affecting the rate of survival.