Volume 4 • Issue 4 • 1000184 J Cytol Histol ISSN: 2157-7099 JCH, an open access journal Research Article Open Access Shapochka et al., J Cytol Histol 2013, 4:4 DOI: 10.4172/2157-7099.1000184 Research Article Open Access Expression of Molecular Markers in Tumours of Patients with Breast Cancer D O Shapochka 1 *, S P Zaletok 1 and M I Gnidyuk 2 1 R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine 2 Ivano-Frankivsk Regional Oncology Dispensary, Ukraine *Corresponding author: D.O. Shapochka, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine, E-mail: shapochka.dm@gmail.com Received July 18, 2013; Accepted August 10, 2013; Published August 12, 2013 Citation: Shapochka DO, Zaletok SP, Gnidyuk MI (2013) Expression of Molecular Markers in Tumours of Patients with Breast Cancer. J Cytol Histol 4: 184. doi: 10.4172/2157-7099.1000184 Copyright: © 2013 Shapochka DO, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract The expression of transcription factor NF-κB (p50 and p65), ER, PR, Her2/neu, Ki-67, p53, Bcl-2 and E-cadherin in tumor tissue of 132 patients with breast cancer was investigated by immunohistochemistry. As a result of researches the correlation between Grade and expression of ER, PR, Bcl-2, Ki-67 and p65-subunit of NF-κB was defned. The level of proliferation was correlated with ER, PR, Bcl-2, p53 and Her2/neu expression. Also the correlation between some of investigated markers was found. Thus, high level of NF-κB nuclear expression was associated with Her2/neu hyperexpression and negative status of ER, PR and Bcl-2. These data may indicate poor prognosis and resistance to chemotherapy in breast cancer patients with activated NF-κB, but it requires further research and retrospective analysis of large number of patients. Keywords: Breast cancer; Receptors of steroid hormones; Her2/neu; NF-Κb; Ki-67; p53; Bcl-2; E-cadherin Introduction Breast Cancer (BC) is by far the most frequent cancer in women, and the main cause of death in women of 35-55 years old. Despite the improvement of diagnostic methods and chemotherapeutic regimes overall 5-year survival of patients is signifcantly depends on the stage of disease and in the period 2000-2005 is 56.2% in Ukraine [1]. Such clinical characteristics as age, menstrual status, tumor size, lymph node status and morphological characteristics of the tumor (histological type, Grade, lymphatic/vascular invasion) traditionally are an important prognostic factors. However, in the last decades understanding of tumor nature has been greatly enlarged by molecular biology researches, which allowed the application of tumor’s molecular features for prognosis of the disease fow. Most molecular markers that are studied today, involved in pathological processes which together determine the ability of cells to malignant growth [2]. Tus, for the entry of normal cells into mitosis is required exogenous growth signal. However, malignant transformation of cells may be accompanied by loss depending on these signals. In breast tumors ofen occurs overexpression of Her2/neu, which is one of a family of receptors Epidermal Growth Factor Receptor (EGFR). Tis family consists of four members: EGFR/ErB1/HER1, c-erbB2/ Her2/Neu, ErB3/HER3 and ErB4/HER4. Tere are 3 main biological efects mediated by EGFR: inhibition of apoptosis, stimulation of proliferation and modifcation of adhesion molecules. Her2/neu overexpression can be detected by immunohistochemical method, or by enzyme-linked immunoassay in circulation. In breast cancer tumors it ofen associates with amplifcation of the gene and can be detected by Real-time PCR and fuorescence (FISH), or Chromogenic in situ Hybridization (CISH). Positive Her2/neu is associated with clinical and morphological parameters of the tumor, indicating the poor prognosis of the disease. Another important process towards malignant transformation of cells is the blockage of apoptosis. Te most common molecular event that leads to this outcome is the inactivation of the protein p53. According to diferent authors, up to 50% of breast tumors have mutations of the p53 gene. P53 is a key component of the defense system, which blocks the formation of atypical cells. Protein p53 is activated in response to DNA damage, oncogene activation, hypoxia, oxidative stress, viral infection and other anomalous processes leading to cell cycle arrest and damage repair or apoptosis. Mutations in the p53 gene ensuring the increase of genetic instability, high levels of proliferation and apoptosis blockade. Tere are two basic methods for determining the status of p53 in tumors: genetic (eg sikvens or PCR) and IHC analysis (which was used in this study). According to the literature, positive nuclear reaction with p53 in 90-100% of cases corresponds missens mutations of p53 gene that determine mutant immunophenotype [3]. But the negative reaction with antibodies against p53 only in 80% of cases indicates the absence of mutations in the gene, while in 20% of cases protein is just do not expressed [3]. In breast tumours, as in tumours at other sites, the presence of mutant p53 is associated with a decrease in sensitivity to therapy and occurrence of aggressive disease. An important regulator of apoptosis is the family of proteins Bcl. Some members of this family are inhibitors of apoptosis (Bcl-2, Bcl-Xl), the rest - inductors (Bax, Bad). Te most important predictive value for BC among this family has Bcl-2. Tis protein inhibits release of mitochondrial cytochrome c and apoptosis-inducing factor [4] as well as lipid peroxidase reaction in the mitochondrial membrane [5], which leads to inhibition of apoptosis. Te level of Bcl-2 in cells is regulated by p53 protein on the principle of feedback, thus the co-expression of these factors is very rare [6]. Many authors confrmed the correlation between overexpression of Bcl-2 and positive status of steroid hormone receptors; negative – of p53 and Her2/neu; low level of proliferation [7,8]. In addition, overexpression of Bcl-2 is associated with increased overall and disease-free survival of patients with breast cancer [7-9]. Journal of Cytology & Histology J o u r n a l o f C y t o l o g y & H i s t o l o g y ISSN: 2157-7099