Estimation of association of clinical-pathological features of tumor process with results of clinical-genealogical examination of patients with ovarian and breast cancer — carriers of mutation 5382insC in BRCA1 gene

Summary. Complex clinical-pathological, clinical-genealogical pathomorphological, molecular-genetic examinations of 23 patients with ovarian cancer (OC), І–ІV stages (FIGO classification) and in 21 patient with breast cancer (BC), stages І–ІІ (according to TNM) were carried out. Analysis of genomic DNA from peri­pheral blood (before treatment) was performed to determine mutations 185delAG and 5382insC in BRCA1 gene, and mutation 6174delT in BRCA2 gene. Results of clinical and molecular-genetic examination of DNA from peripheral blood of 55 healthy women without oncologic pathology in anamnesis were used as a control. Excised tumors were analyzed for histological type and differentiation grade. In BC patients molecular tumor subtype was determined by immunohistochemical examination of expression of hormone receptors to estrogene (ER) and progesterone (PR), and human epidermal growth factor type II (HER2/neu). The results demonstrated that in patients with OC and BC from the families with aggregation of tumor patho­logy the differences in reproductive-menstrual function status were not found. In genomic DNA from peripheral blood only the mutation 5382insC in BRCA1 gene was determined. Basing on the obtained results clinical, clinical-pathomorphological tumor characteristics, and its association with the results of clinical-genealogical and molecular-genetic examinations were analyzed individually for every patient with mutations in BRCA1 gene. This mutation was observed in 3 (13%) of 23 patients with serous OC and 4 (19%) of patients with infiltrative ductal BC of luminal molecular subtype. In both groups of examined patients there were more maternal relatives with cancer than paternal relatives with cancer. In women from control group mutations in BRCA1 and BRCA2 genes were not found. Association of the mutation 5382insC in BRCA1 gene with development of hereditary syndrome of OC/BC and primary-multiple tumors of female reproductive system organs was confirmed.