English
Abstract
Breast cancer is one of the most common malignancies worldwide, affecting 2.3 million and causing 670,000 deaths in women annually. However, data indicate that the risk of developing breast cancer decreases with pregnancy at a young age, and each subsequent pregnancy further reduces the risk by approximately 10%. One of the characteristics inherent in both the mammary gland epithelium in pregnant women and luminal epithelial adenocarcinomas is the increased expression of NIS—the sodium/iodide symporter, whose defective cytoplasmic forms possess pro-oncogenic properties. Therefore, the analysis of the degree of influence of pregnancy on NIS expression in breast cancer cells is of medical interest. The aim of this study is to conduct a comparative morphological analysis of NIS expression in breast cancer cells according to the number of pregnancies of each patient. This study included 161 patients with triple-negative breast cancer who visited the P.A. Herzen Moscow Oncology Research Institute from 2020 to 2023. Immunohistochemical examination was performed using antibodies to NIS. The gravidity status of women was determined based on provided medical documentation. The degree of NIS expression was assessed using a modified Gainor scale. Statistical analysis was performed using mean and standard deviation (SD) depending on the normality of the distribution (Lilliefors test: p > 0.20); a p-value ≤ 0.05 was considered statistically significant. The degree of correlation between variables was assessed using Kendall’s tau rank correlation coefficient. A weak to moderate negative correlation (τ: −0.369) was found between the number of pregnancies and the degree of NIS expression in triple-negative breast cancer cells. In patients with triple-negative breast cancer, a weak to moderate negative correlation was found between the degree of NIS expression and gravidity status. The discovered phenomenon is likely due to the terminal differentiation of the mammary gland epithelium that occurs during pregnancy. This may potentially indicate the suppression of pro-oncogenic properties of atypical cells developed from the epithelium that has undergone terminal differentiation.
Keywords:
triple-negative breast cancer; sodium/iodide symporter (NIS); breast cancer; pregnancy
1. Introduction
Breast cancer (BC) affects 2.3 million women worldwide and causes 670,000 deaths annually [1]. A distinctive feature of this malignancy is that the main risk factors for BC are non-modifiable. For example, reproductive factors play a key role [2]. The fact is that one of the ontogenetic features of the luminal epithelium of the mammary glands is the variability of its proliferative status depending on the current hormonal background and presence of pregnancies in the patient’s history. Molecular biological studies have demonstrated that even after one pregnancy, the proliferative activity of the epithelium of terminal ductal lobular units decreases many times over, which significantly affects the risk of malignant transformation of these cells [3]. The reason for these changes is cellular terminal differentiation, which in the long term reduces the risk of cancer development [4]. One manifestation of terminal differentiation is a change in the degree of DNA methylation, which is physiologically necessary for the rapid reactivation of specific genes required for cellular and metabolic restructuring of the mammary gland and milk secretion. Thus, in the study by dos Santos et al., it was demonstrated that pregnancy changes the degree of genome methylation due to the activity of the transcription factor STAT5a.
In this case, it is of particular interest to study changes in the biological properties of a tumor depending on the woman’s gravidity. One of the paradoxical manifestations of changes in the functioning of the genetic apparatus of tumor cells is the abnormal expression of the sodium/iodide protein co-transporter—NIS/SLC5A5, which is normally expressed in the epithelial cells of the mammary ducts only in the late stages of pregnancy and during lactation [5]. The main function of this protein is to saturate milk with iodine to maintain and stimulate the activity of the thyroid gland of the newborn, which contributes to the adequate development of the newborn organism [6]. However, in 2000, Tazebay et al. discovered that most breast carcinomas are NIS-overexpressing [7]. Further studies have demonstrated that this is likely an indirect manifestation of genetic mutations characteristic of breast carcinomas/triple-negative breast cancer, leading to hyperactivation of the FOXA1 and PI3K/AKT/mTOR signaling pathways [8,9]. At the same time, the disorganization of the protein synthetic apparatus of tumor cells leads to excessive accumulation in the cytoplasm of pathological forms of the NIS protein, which have pro-oncogenic properties—the ability to stimulate the migration and metastasis of tumor cells; that is, NIS expression itself is a factor potentially capable of influencing the prognosis in each individual patient [10]. However, despite the availability of experimental studies on the role of NIS in tumor biology over the past 20 years, there are no studies on the practical application of NIS expression assessment, and this requires separate attention.
The article is reprinted from MDPI, original link:https://www.mdpi.com/1422-0067/26/20/9947
The FAI climbed 5.9 percent year-on-year in the first 11 months of 2018, quickening from the 5.7-percent growth in Jan-Oct, the National Bureau of Statistics (NBS) said Friday in an online statement.
The key indicator of investment, dubbed a major growth driver, hit the bottom in August and has since started to rebound steadily.
In the face of emerging economic challenges home and abroad, China has stepped up efforts to stabilize investment, in particular rolling out measures to motivate private investors and channel funds into infrastructure.
Friday's data showed private investment, accounting for more than 60 percent of the total FAI, expanded by a brisk 8.7 percent.
NBS spokesperson Mao Shengyong said funds into weak economic links registered rapid increases as investment in environmental protection and agriculture jumped 42 percent and 12.5 percent respectively, much faster than the average.
In breakdown, investment in high-tech and equipment manufacturing remained vigorous with 16.1-percent and 11.6-percent increases respectively in the first 11 months. Infrastructure investment gained 3.7 percent, staying flat. Investment in property development rose 9.7 percent, also unchanged.