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The treatment of colon cancer with a mesenchymal-like phenotype poses a great challenge. Purpose of the study: to research expression of FRMD6, ZEB1, HTR2B, CDX2 in the primary tumor tissue with relation of the clinical and pathological features of colon cancer. Material and methods. a combined analysis of the expression of FRMD6, ZEB1, HTR2B, CDX2 with pathological criteria was performed in 100 patients with T1–4bN0–2bM0 colon cancer. Results of the study show that tumors with mesenchymal signs are characterized by a large size of the primary tumor, a high grade of differentiation, regional metastases, and eventually advanced stage of the disease. The frequency and expression levels of FRMD6, ZEB1 and HTR2B are depended of grade of adenocarcinoma. in cases with positive expression and a high percentage of expression of these proteins in the cancer cells, the degree of tumor morphological anaplasia increases. Conclusion. The study made it possible to reveal the relationship of IHC markers (FRMD6, ZEB1, HTR2B, CDX2) with tumor characteristics that determine the outcome. The studied markers may have prognostic and predictive value in treatment approaches of colon cancer.

The purpose of the study was to generalize information regarding the molecular and biological mechanisms involved in the resistance to endocrine therapy with aromatase inhibitors in patients with luminal breast cancer. Material and Methods. The literature search was conducted using Medline, Cochrane Library, Elibrary and PubMed databases. Results. The review highlights the results of international studies on molecular and biological characteristics of breast tumors and their relationship with the effectiveness of hormone therapy. Particular attention was paid to the description of modern studies on ROR1 and BMI-1 proteins and their contribution to the development of tumor resistance to treatment. Conclusion. The analysis of the world literature confrms the relevance of studying the molecular and genetic characteristics of tumor tissue in patients with luminal breast cancer. The data obtained were compared to the clinical course and response to hormone therapy in order to standardize them for implementation in everyday practice as the “gold standard of diagnosis”.

Purpose of the study: to review the available data on the heterogeneity of colon cancer and to assess the prognostic significance of colon cancer subtypes.Material and Methods. Medline, PubMed, Cochrane library, elibrary databases were used to identify studies that characterized the current view on the problem of choosing the optimal postoperative treatment for colon cancer.Results. the review showed the results of international studies of colon cancer subtypes based on complex multomics characteristics. Particular attention was paid to the description of modern studies on the search for prognostic markers for colon cancer. The relevance of the study of immunohistochemical markers was confirmed by the analysis of the world literature. the outcomes will make it possible to classify colon cancer into molecular subtypes in real clinical practice and, as a consequence, significantly improve the effectiveness of adjuvant therapy.

Background. The identification of predictive molecular markers of luminal breast cancer will help to assess the risk of developing distant metastases and determine a personalized approach to predicting the outcome of the disease during hormone therapy.The aim of the study was to investigate the relationship between the transcription factors GATA3, FOXA1, and ELF5 in the tumor and the occurrence of distant metastases in patients with luminal subtype of breast cancer during adjuvant hormone therapy.Materials and methods. The study included 101 patients with breast cancer (aged from 30 years to 81 years, average age (54.8 ± 10.3) years), with stages T1–4N1–3M0 of the disease. The follow-up period was at least 5 years. The inclusion criteria for the study were luminal molecular genetic subtype of the tumor and lack of preoperative treatment. The exclusion criterion was stage IV disease. The study of transcription factors was carried out by the immunohistochemical method using polyclonal antibodies to GATA3, FOXA1, and ELF5, manufactured by Flarebio (Austria).Results. Low expression of FOXA1 and ELF5 in the tumor was associated with the development of distant metastases (p = 0.000015 and p = 0.000002, respectively). In addition, it was found that high incidence of hematogenous metastases was associated with heterogeneous expression of FOXA1 (χ2 = 6.42; p = 0.01) and ELF5 (χ2 = 14.46; p = 0.0001) in the tumor. No similar differences were found in the study of GATA3 expression.Conclusion. The level of expression of transcription factors FOXA1 and ELF5 and their distribution in the primary tumor can be considered as potential molecular markers in assessing the risk of hematogenous metastasis in patients with luminal breast cancer.

Background. It is generally accepted that crosstalk between the growth factor receptor and ER pathways implicated in tamoxifen resistance. The aim of the study was to examine the relationship between mRNA level, protein expression and gene polymorphism of the EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer. Materials and methods. The study included 95 breast cancer patients who had received adjuvant tamoxifen, of which 31 patients developed recurrence/metastasis after tamoxifen treatment (tamoxifen resistance group), 64 patients did not develop any diseases progression (tamoxifen sensitive group) during the 5 years of follow-up. Genotypes for ESR1 (rs2077647, rs2228480, rs1801132), EGFR (rs1468727, rs2227983), AKT1 (rs1130233) and PTEN (rs11202592) were analyzed using a TaqMan assay. Using reverse transcription-PCR, the relative expression of mRNA for ESR1, EGFR, AKT1 and PTEN was determined. ERα, EGFR, Akt (pS473) and PTEN expression level was evaluated using immunohistochemistry. Progression-free survival (PFS) was estimated by Kaplan – Meier analysis. Results. The minor allele of ESR1 rs2077647 was more prevalent in tamoxifen sensitive tumors compared to tamoxifen resistant tumors (p = 0.044). We found high AKT1 mRNA expression level in tamoxifen sensitive group compared with tamoxifen resistance patients (7.27 ± 5.29 and 0.02 ± 0.01, respectively, p = 0.014). ESR1 rs2228480 was significantly associated with tamoxifen resistance (p = 0.028). EGFR and Akt (pS473) protein expression level was significantly higher in the tamoxifen resistance group compared to tamoxifen sensitive breast cancer patients (p = 0.006 and 0.037, respectively). Patients carrying mutant genotypes of ESR1 rs2228480 had a poorer progression-free survival than those carrying wild and heterozygous variants (log rank p = 0.043). Positive EGFR tumor expression as well as positive Akt (pS473) expression were significantly associated with shorter PFS (log rank p = 0.014 and 0.048, respectively). Conclusion. Polymorphic sites of the ESR1 gene, AKT1 mRNA expression, EGFR expression level and Akt (pS473) protein expression can be potential molecular markers associated with tumor sensitivity/resistance to tamoxifen treatment.

Currently, the study of the markers of cell differentiation, proliferative regulators, and molecules involved in the development of drug resistance mechanisms in breast cancer is extremely important. The transcription factor GATA3 plays an essential role in the differentiation and proliferative activity of luminal breast cancer cells, being a tumor suppressor. The GATA3 positive expression is most frequently observed in invasive carcinoma of no special type. High expression of GATA3 is associated with low-grade ER-positive cancer with a favorable prognosis. Low GATA3 expression is observed in patients with high-grade and hormone receptor-negative cancer. The study of GATA3 expression is necessary for understanding the development of drug resistance mechanisms and developing approaches to overcome them as well as for determining the response to hormone therapy. Aim. The present study was undertaken to study the expression characteristics of the transcription factor GATA3 in patients with luminal breast cancer and to evaluate their relationship with the parameters of lymphogenous metastasis. Material and methods. The study included 64 patients with stage T1–4N1–3M0 invasive breast cancer. The primary tumor tissue and all removed lymph nodes were morphologically examined. The diagnosis was established according to the WHO criteria (2012). Results. Low GATA3 expression was associated with a high risk of lymph node metastases, while high GATA3 expression was associated with the absence of lymph node metastases. Heterogeneous GATA3 expression was associated with high risk of lymph node metastasis, and as a consequence, with poor prognosis. Conclusion. The relationship between the expression of GATA3 protein and lymphogenic metastasis in patients with luminal breast cancer was found.

Introduction. The crosstalk between the estrogen and growth factor receptors signaling may play an important role in the resistance to endocrine therapy. The aim of the study was to examine the relationship between the protein and receptor gene expression of transforming growth factor β type I (TGF-βRI) and its polymorphism with progression of luminal breast cancer patients treated by adjuvant tamoxifen. Material and methods. The study included 105 patients with luminal breast cancer (T1-3N0–3M0), who had received adjuvant tamoxifen at a dose of 20 mg/day for at least 5 years. Patients who developed distant metastasis or recurrence after tamoxifen therapy were defined as tamoxifen resistance (TR) group, while distant metastasis-free patients were analyzed as tamoxifen sensitive (TS) group. TGF-βRI expression level was evaluated using immunohistochemistry. TGF-BRI gene expression and genotypes for rs334354 SNP were detected by a Real-time PCR. Results. We found high TGF-βRI gene expression in patients with luminal A subtype compared with luminal B breast cancer (p=0.050). The Int7G24AA and Int7G24A mutant carriers were more prevalent in luminal A breast cancer patients (p=0.019 and p=0.007, respectively). TGF-βRI protein expression level was significantly higher in the tamoxifen sensitive group compared to tamoxifen resistance breast cancer patients regardless of molecular subtypes (p=0.043). There was a trend for a tamoxifen sensitivity among luminal B breast cancer patients with a high TGF-βRI protein expression (p=0.090). Conclusion. TGF-βRI protein expression level can be a potential molecular marker of tamoxifen resistance in luminal breast cancer patients.

The purpose of the study: to evaluate the response to neoadjuvant anthracycline-based chemotherapy depending on the presence of deletions and amplifications of different chromosomal loci and the expression level of topoisomerase 2а in tumor tissue of breast cancer patients. Materials and methods. The study included 46 patients with stage T2–4N0–3M0 breast cancer, who received 2–6 cycles of neoadjuvant chemotherapy with FAC and CAX regimens. Results. The relationship between the expression level of Тор2а>5, deletions of ABCB1, ABCB3, 18р11.21, 11q22.1 loci and amplification of 1q24.1-43 and the response to preoperative treatment was found. Of the 34 patients having at least one of these markers in the tumor tissue, 85.3 % of them demonstrated partial response to neoadjuvant chemotherapy (> 50 % reduction of tumor) and 14.7 % had stable disease and disease progression. No above markers were found in the tumor tissue of 12 patients, who did not respond to preoperative treatment. Conclusion. High levels of Тор2а>5 expression, deletions of ABCB1; ABCB3; 18р11.21; 11q22.1 loci and 1q24.1-43 amplification were shown to be predictive markers of response to neoadjuvant anthracycline-based chemotherapy. The presence of at least one of these markers allowed us to predict response to preoperative treatment in 85 % of cases.

The present study was undertaken to determine the relationship between tumor response to neoadjuvant chemotherapy including capecitabine and long-term treatment outcomes in patients with operable breast cancer. material and methods. The study included 139 patients with stage T2-3N0-2M0 breast cancer, who received 2-4 courses of neoadjuvant chemotherapy with the FAC and САХ regimens. Immediate response was assessed using the RECIST criteria. Long-term treatment outcomes and metastasis-free survival rates were evaluated using the Kaplan-Meier method. Results. By assessing the relationship between long-term treatment outcomes and the immediate response to adjuvant chemotherapy with capecitabine, we identified the group of patients with tumor regression ≥ 80%, who had the 7-year metastasis-free survival rates similar to those observed in patients with pathologic complete response. Such factors as the primary tumor size, regional tumor spread, receptor status of tumor tissue and the number of chemotherapy courses were found to have no impact on the frequency of hematogenous metastasis. Conclusion. The results obtained indicate that ≥ 80% tumor regression after neoadjuvanch chemotherapy including capecitabine can be considered as a predictive parameter for assessing metastasis-free survival in patients with operable breast cancer.

The present study has found significant heterogeneity of luminal A breast cancer group, which is manifested by differences in relationship between the frequency of lymphogenic metastasis and morphologic and molecular-biological parameters of the primary tumor. The frequency of regional metastases has appeared to relate to the presence of microalveolar structures in infiltrating component of invasive ductal breast cancer and to its phenotypic variety only in menopausal patients. It can be evidence of differences in tumor pathogenesis in patients with different state of menstrual function even within one molecular-genetic tumor group. It is important to emphasize that the different variantsof clinical behavior of luminal A breast cancer are associated with morphological parameters of the tumor, allowing one to easily obtain the additional information during histological examination of bioptic material for predicting clinical course of luminal-type A breast cancer.

Luminal A breast cancer has been shown to be characterized by the marked morphological heterogeneity. It is manifested by the variety of the infiltrative component structure of the primary tumor in which different structure types vary widely. The frequency of metastaticinvolvement of lymph nodes has appeared to associate with a variety of infiltrative component of the tumor and the presence of microalveolar structures in it. Neither morphological patterns of the lesion nor parameters of lymphogenic metastasis were associated with hematogenous dissemination, thus allowing no them to be considered as prognostic criteria.

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.