Pvuii Polymorphism in the Estrogen Receptor Αlpha Gene as an Indicator for Surgical Treatment in Patients With Benign Mammary Dysplasia

Abstract

The paper presents the results of studying the relationship between the genetic characteristics of the individual and the phenotypic manifestations of benign mammary dysplasia. Data were provided on the role of PvuII polymorphism in the development of breast tissue proliferation through the mechanisms of EsRα overexpression; this can be used as a marker for surgical treatment necessity. The objective of the work was to develop criteria for the diagnosis of proliferative benign mammary dysplasia on the basis of immunohistochemical and molecular genetic studies to substantiate the indications for surgical treatment. Materials and methods: The study involved 84 patients: 66 (78.6%) subjects from Sumy and 18 (78.6%) subjects – from the Sumy region. The mean age of the subjects was (32.3 ± 1.1) years, with the range of 16–62 years. Among the subjects, 82 (97.6%) were women with BMD and 2 (2.4%) were men who suffered from nodular gynecomastia. The burdened history of breast cancer in close relatives was reported in 33 (39.3%) individuals. Apart from a profound assessment of history data, the clinical course of the disease and comorbidities were studied. Instrumental and laboratory tests were performed. The morphological and immunohistochemical features of dissected tissues, as well as genetic differences of patients, were studied. By age, the subjects were divided into three groups: the first group (under 21 years) included 15 (17.8%) individuals, the second group (22–39 years) – 43 individuals (51.2%), the third group (over 40 years) – 26 individuals (31.0%). Results: The frequency of allelic variants of the EsRα gene PvuII polymorphism in patients with a proliferative form of benign mammary dysplasia was distributed as follows: T/T genotype - 27.4%, T/C genotype – 51.2%, C/C genotype - 21.4%. The most significant clinical predictors in patients with proliferative benign mammary dysplasia were: mastodynia (χ2 = 11.444; P = 0.003), decreased BMI of up to (21.17 ± 1.06) kg/m2 (F = 5.020; P = 0.009), prolonged menstruation of up to (5.67 ± 0.30) days (F = 3.017; P = 0.055). A group of patients whose mammary cells do not have estrogen receptors was identified. Since prescription of antiestrogens as a means of prevention in patients of this group will not be effective, such patients should be offered surgery as an option for further atypia prevention. Conclusions: Additional studies of EsRα expression and the pathological C-allele of the EsRα gene PvuII polymorphism have been found to play an important role as criteria for the diagnosis of proliferative benign mammary dysplasia that substantiate indications for surgical treatment. The specificity of the histological structure of tissue, the features of the cell receptor apparatus, and genetic predictors are important indicators for understanding the causes and mechanisms of proliferation in BMD. The calculated results indicate that BMDs begin to develop against the background of retained menstrual cycle and reproductive function, which indicates a crucial role of local estradiol receptors status in breast tissue in the development of proliferation foci in BMD. Hormone imbalance contributes to morphofunctional changeover. The results of the study will serve as the basis for identifying patients prone to the development of BMD proliferative forms and their timely surgical treatment to prevent the development of malignancy. Keywords benign mammary dysplasia, PvuІІ polymorphism in the estrogen receptor α gene, tissue proliferation.