Uticaj molekularnih karakteristika invazivnog duktalnog karcinoma dojke na pojavu lokoregionalnih metastaza
Committee membersStojanović, Miroslav
Janković Veličković, Ljubinka
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Breast cancer (BC) is the most common malignant tumor in female population and the most common cause of death from malignant diseases in women. The most recent literature data have suggested that there is a small population of cancer stem cells, comprising less than 1% of primary tumors, which are responsible for the development of metastases and disease progression. Breast cancer stem cells (BCSCs) have the ability to self-renew and to create a dominant population of cancer cells. The BCSCs phenotype is specific and characterized by the expression of nuclear and membrane pluripotency factors (molecular markers). In this paper we investigated the expression of markers with stem cell properties (KLF4, SOX2, OCT3/4, EZH2, CD44, CD117) in the cancer cells of invasive ductal breast cancer and their association with clinical-pathological parameters and molecular tumor subtype, aiming to evaluate their impact on the occurrence of locoregional matastases. The results of this study showed that... tumor size (T4), higher Ki-67 index, high OCT3/4 and EZH2 expression, increased number of highly expressed nuclear markers, and increased number of altered markers were significantly associated with locoregional disease spread. A high expression of OCT3/4 and EZH2 in invasive ductal breast cancer was predictive of axillary metastases. An increased number of metastatic axillary lymph nodes was significantly associated with reduced ER and PR scores, high expression of OCT3/4, EZH2 and SOX2, with an increased number of nuclear markers with high expression, coexpression of all nuclear markers, coexpression of membrane markers CD44 and CD117, and the increased number of altered markers. Coexpression of all nuclear, as well as CD44 and CD117 markers, was predictive of the increased number of metastatic axillary lymph nodes. T4 stage, reduced ER and PR scores, increased expression of OCT3/4, EZH2 and SOX2 had a significant impact on the increased percentage of metastatic axillary lymph nodes, as well as a greater number of nuclear markers with high expression, coexpression of all nuclear markers, coexpression of highly expressed membrane markers, and a greater number of altered markers. Tumor size, increased number of highly expressed nuclear markers, and CD44 and CD117 coexpression were predictive of a greater percentage of metastatic lymph nodes. Since the development of lymphonodal metastases is a key event in the progression of breast cancer, with a deeper knowledge of primary tumor heterogeneity and using standard and new molecular markers, it is important to identify the patients at risk for the development of metastases.