Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX.Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients’ blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses.Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression.Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.
Relevance. PIK3CA belongs to the top three most frequently mutated genes in breast cancer (BC), especially in estrogen receptor (ER) positive, HER2 negative BC subtype. With an approval of selective PI3K-alpha inhibitor, alpelisib, this alteration has become actionable in ER+HER2- tumors. The frequency and spectrum of PIK3CA alterations in various cohorts is affected by a number of factors, including the distribution of BC expression subtypes, histological types, patient age, and even ethnicity. Aim. Aim of the current study was to characterize the frequency and spectrum of PIK3CA alterations in Russian BC patients. Materials and methods. The analysis of PIK3CA exon 7, 9 and 20 mutations was performed in a cohort of Russian ER+HER2- BC patients by a combination of high-resolution melting analysis, allele-specific PCR, and digital droplet PCR. Results. PIK3CA lesions were identified in 62/206 (30%) patients. Noteworthy, 59/62 (95%) of the identified variants were represented by the three most common p.E542K, p.E545K, and p.H1047R substitutions. The analysis of clinical and morphological characteristics revealed the trends towards association of PIK3CA mutations with older age and more frequent metastatic lung involvement. Conclusion. The obtained data on the frequency and spectrum of PIK3CA somatic aberrations can be helpful when organizing molecular genetic testing of breast cancer patients and using PI3K inhibitors in Russian population.
Among the multiple primary malignant tumors, breast cancer is the most common and in most cases it is combined with the second mammary gland, uterine body, stomach, colon, skin and ovary. Breast angiosarcoma is a very rare disease with unfavorable prognosis. Radiation therapy to the area of the breast is considered to be the main risk factor for the radiation-induced angiosarcoma. Diagnosis is based on the clinical aspect, the results of morphological and immunohistochemical findings. There are no uniform standards for the treatment of this pathology; a surgical method, systemic therapy, and radiation therapy are used. The article presents a clinical case of a female patient born in 1952, who was diagnosed with synchronous multiple primary cancer in 2014: stage 2A left breast cancer (cT2N0M0); bladder cancer stage I (cT1cN0M0). After the complex treatment, the patient received adjuvant endocrine therapy with Tamoxifen. In December 2018, single bluish formations appeared in the area of the postoperative scar, followed by a rapid growth of formations on the skin within a month, with a tendency to merge and necrosis. The patient was sent for biopsy of the formations with suspected recurrence of the disease. Immunomorphological patterns correspond to the angiosarcoma in the skin of the mammary gland. A simple mastectomy was performed. After 3 months, growth of angiomyosarcoma in the soft tissues of the anterior chest wall continued. Excision of the tumor in the soft tissues of the chest was performed and the patient underwent postoperative course of radiation therapy with a single focal dose (SFD) 2.5 Gy, total boost isodose of 50 Gy. At follow-up examinations held from January to December 2021, there is no evidence for continued growth and recurrence of the disease. The presented clinical observation demonstrates the experience of diagnostics and treatment of radiation-induced angiosarcoma in the patient with multiple primary synchronous lesions of the breast and bladder.
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