Pesquisa de marcadores circulantes em lesões impalpáveis da mama: alterações somáticas e epigenéticas

Abstract

Early detection of breast cancer increases the chances of cure, but identification of initial and impalpable lesions is still a challenge. Mammography is public right of women only after age 50 according to the MS, which contributes to late diagnosis, with longer palpable lesions and advanced stage. In addition, the image processing is a constant target of misinterpretation and misleading results. The search for circulating tumor markers has been widely explored in an attempt to minimize agressive treatments and contribute to early detection of breast cancer. The difficulty in practice is determine the molecular markers that would be able to differentiate authentic benign of premalignant and malignant lesions. Breast cancer is considerably heterogeneous and with variable clinical outcomes, it is not possible to determine the evolution of the breast lesion and the phenotype of tumor cells. Tumor suppressor genes have become the main candidate markers, because the frequency of abnormalities detected in breast cancers. The aim of the study was to investigate among the set of suppressor genes, those with higher rates of somatic mutations and epigenetic changes contained in carcinogenic initial process. Analysis of the coding region of TP53 (4-9), and CDKN2A (1-3) genes was carried out on 62 samples, 21 of which were benign and 41 malignant. No mutation was found by direct sequencing these genes. Epigenetic assessment of TP53, CDKN2A and ATM genes in non palpable lesions, blood and saliva showed variants results. Among the 62 breast lesions assessed 1 (1.6%) was positive for p14ARF, 3 (4.8%) for p16INK4a and 33 (53.2%) for ATM. Of the 39 DNA samples from peripheral blood, 10 (26%) were positive for p14ARF, 17 (44%) for p16INK4a and 16 (41%) for ATM. Saliva cases, 1/39 (2.6%) had methylation to p14ARF, 6/39 (15.4%) for p16INK4a and 9 (23%) for ATM. Statistical analysis revealed no significant values compared the clinical variables of the patients. Of the lesions conferring with early stage of breast carcinogenesis and corroborate with the data of literature which somatic mutations are frequent in advanced lesions, with histologic subtypes and prognosis more aggressive. Already epigenetic findings, although no association of statistical significance was found, are determinants the methylation frequency in secondary fluid and awaken the need for research on a sample size greater that the analyzed.