Abstract
Objective:In order to enhance the prognostic benefit of new molecular markers, the aim of this study was to identify possible association of axillary lymph node (ALN) status and pN with clinicopathological characteristics and expression of EZH2 and CD44 in invasive ductal carcinoma (IDC) of the breast.Methods:The investigation included 106 patients with IDC who had undergone radical mastectomy at the Clinic of Endocrine Surgery in Nis. Clinicopathologic parameters and immunohistochemical expression of EZH2 and CD44 in primary IDC were investigated in relation to ALN status and pN.Results:Our univariate analysis established that T3-T4 stage, high EZH2, and high EZH2 with ER- were associated with ALN metastasis (p=0.014; 0.003; 0.013). Decreased probability for ALN involvement was found with T1 stage, and low EZH2 with ER+ (p=0.032; 0.022). Multivariant analysis established that high EZH2 in cancer cells was associated with high risk for ALN metastases (p=0.004); T1 tumors were associated with low risk (p=0.037). Higher pN was associated with high EZH2, high EZH2 with ER-, as well as an advanced clinical and disease stage (p=0.006; 0.001; p=0.002, 0.001). Lower pN was associated with ER+, and ER+ with low EZH2 (p= 0.004; 0.012). CD44 was not associated with ALN involvement, nor with pN.Conclusions:This study revealed association of EZH2 with ALN metastases, where disease stage and expression profiles of EZH2 and ER may have affected regional pN.
Highlights
Breast cancer (BC) is the most diagnosed type of cancer in women throughout the world, and it has the second highest mortality rate in this group, after lung cancer.[1,2,3] Invasive carcinoma of no special type is the most common histologic type of invasive BC, comprising 75% to 80% of newly diagnosed invasive tumors.[2]
In order to enhance the prognostic benefit of new molecular markers, the aim of this study was to identify possible association of axillary lymph node (ALN) status and pN with clinicopathological characteristics and expression of Enhancer of Zeste Homolog 2 (EZH2) and CD44 in invasive ductal carcinoma (IDC) of the breast
Investigation of relationships between ALN status and investigated parameters showed that ALN metastases were closely linked to tumor stage (p=0.012), clinical stage (p=0.019) and expression of EZH2 (p=0.003)
Summary
Breast cancer (BC) is the most diagnosed type of cancer in women throughout the world, and it has the second highest mortality rate in this group, after lung cancer.[1,2,3] Invasive carcinoma of no special type (ductal NOS) is the most common histologic type of invasive BC, comprising 75% to 80% of newly diagnosed invasive tumors.[2]. Studies on human tumors show that EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, including BC, where is consistently associated with poor prognosis and aggressive behavior, including invasiveness and metastatic potential.[7,8,9] EZH2 promotes BC progression by transcriptional repression of tumor suppressors and by maintaining the cells in a stem cells state.[7] CD44 is a well-known marker with a role in promoting tumorigenesis of BC, including transformation, growth, cell invasion and motility, and is a marker of BC stem cells.[7] In order to enhance the prognostic benefit of standard and new molecular markers on the occurrence of metastases in BC, the expression of EZH2 and CD44 was examined
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