Breast cancer (BC) is a heterogeneous pathology, not only in terms of clinical, pathological and molecular biological features, but also has certain characteristics of the tumour process that determine its aggressiveness. A number of studies have demonstrated that bone matrix remodelling proteins are useful predictors of breast cancer aggressiveness. Osteopontin (OPN) promotes tumour aggressiveness by enhancing epithelial-mesenchymal transition (EMT), while osteonectin (ON) is involved in extracellular matrix remodelling and creates favourable conditions for metastatic spread of transfected cells. However, the aggressiveness of BC is not only influenced by the stage or molecular biological characteristics of the malignant process, but also by metabolic changes in the human body. The metabolic syndrome (MetS), particularly hyperinsulinemia, obesity and chronic inflammation, can increase the expression of these proteins, which may contribute to a more aggressive course of BC. 

Aim. To analyse the relationship of OPN and ON expression with clinicopathological characteristics of BC patients with distant metastases in combination with the presence of MetS signs and to determine their significance in predicting the aggressiveness of the tumour process. 

Materials and Methods. A collection (55 samples) of tumour tissue from patients with metastatic breast cancer (MBC) was selected for this study. Patient groups were formed based on the analysis of their clinical data and medical history, and were assessed according to the recommendations of the International Diabetes Federation (IDF, 2005). Patients with signs of MetS were assigned to the MetS+ group and those without metabolic disorders to the MetS- group. All patients were randomised according to age (≥ 50 years), disease stage (clinical stage IV) and were defined as those who had not received prior neoadjuvant treatment. All samples were subjected to immunohistochemical analysis to determine the expression of matrix proteins: OPN (clone: ab21 4050, AbCam, UK) and ON (polyclonal: osteonectin, Vitro MD, Spain). Conventional clinical, morphological, immunohistochemical, medical and mathematical statistical methods were used. 

Results. An increase in the level of OPN expression (265.6±7.7 H-score, p<0.05) was observed in the tumoral tissue of patients in the MetS+ group of category N3, against the background of a decrease in the level of ON expression (123.2±7.7 H-score, p<0.05). Invasive lobular carcinoma (ILC) tissue from patients in the MetS+ group was characterised by a significant decrease in the level of OPN expression (H-score 219.4±8.4) and an increase in ON expression (H-score 150.4±5.4). However, in the MetS group of patients, a similar ratio of matricellular proteins was found in the invasive breast cancer no specific type (IBC NST) tissue, corresponding to values of 229.9±8.6 and 162.1±5.9 H-score points for OPN and ON, respectively. It was found that ON expression in poorly differentiated BC tissue was decreased in the MetS+ group compared to the MetS- group (138.4±8.9 and 157.3±9.5 H-score points, respectively, p<0.05). It was also shown that the group of MetS+ patients with tumours of luminal A, B or Her2/neu positive subtypes was characterised by significantly lower ON expression (140.2±7.8, 119.3±10.2, 110±7.7 H-score points, p<0.05) compared to the expression levels in tumour tissue of similar subtypes in the MetS- group (158.3±7.2, 151.3±7.2, 171±7.8 H-score points, p<0.05). In addition, ON expression in the tumour tissue of BC with metastatic liver damage was significantly lower in the MetS+ group compared to patients in the MetS- group (146.2±9.1 and 161.7±6.3 H-score points, respectively). 

Conclusions. The data obtained demonstrate the relationship between the expression of matrix proteins in the tissue of breast cancer with diagnosed distant metastases and the aggressiveness of the tumor process and indicate the prospects for further studies of their prognostic value in the presence of MetS.

Anastasiia Neborets is a medical doctor of laboratory and PhD student at the R. E. Kavetsky Institute of Experimental Pathology, Oncology and  Radiobiology of the National Academy of Sciences of Ukraine. In 2016 Anastasiia graduated from the Bogomolets National Medical University (Kyiv) and after completing an internship in Laboratory Diagnostics, she has been working in the cytopathology department of the National Cancer Institute (Kyiv). She is engaged in cytological diagnostics of benign and malignant tumors of various localisations (gynaecological and non-gynaecological pathology). In postgraduate studies since 2018, MD Anastasiia has been dealing with the problem of breast cancer in postmenopausal patients with metabolic syndrome. The results of her own research are published in specialised periodicals in Ukraine, as well as in journals indexed by Scopus and Web of Science. She regularly undergoes additional training to improve her microscopy skills. She actively participates in national and international conferences to share her knowledge.