Altered expression of β-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma

Abstract

The aim of the study was to evaluate the immunoexpression of E-cadherin, β-catenin, and Ki-67, as well as the promoter methylation of E-cadherin gene in epithelial ovarian cancer (EOC), as well as to find a possible relationship between the immunoexpression and hypermethylation. Promoter methylation was studied using methylation-specific PCR in 86 malignant cases, 14 low malignant potential (LMP) tumors and 19 benign cystadenomas. Immunohistochemical expression was carried out in 64 malignant cases, 8 LMP tumors, and 11 benign cystadenomas. Immunoexpression of E-cadherin was reduced in EOC, while 100 % expression was seen in LMP tumors and benign cystadenomas. An interesting observation was the nuclear expression of E-cadherin in a high percentage of cancers, which showed a positive correlation with Ki-67. Β-Catenin expression showed heterogeneous localization with increased nuclear localization, which was significantly higher in cases that did not express E-cadherin. Promoter methylation of E-cadherin was 36, 14, and 11 % in EOC, LMP tumors, and benign cystadenomas, respectively. Our results suggest that reduced expression of E-cadherin is associated with promoter methylation of E-cadherin gene, in addition to providing evidence for the aberrant nuclear localization of E-cadherin in EOC.

EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma

“…Consequently, most patients have reached advanced stage at the time of diagnosis [3]. Despite new diagnostic and surgical advances, and development of chemotherapeutic regimens, the overall 5-year survival for women with advanced stage epithelial ovarian cancer has remained approximately 12% over the past 40 years [4]. Ovarian serous carcinoma (OSC) is a common ovarian epithelial malignancy, which has traditionally been graded as high, moderately, and poorly differentiated, indicating that it is a homogeneous disease in the position of pathogenesis.…”

BRCA1, Ki67, and β-Catenin Immunoexpression Is Not Related to Differentiation, Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian Carcinoma

“…A-Catenin gene mutations lead to the stabilization of this protein, which resists physiological degradation and is found in carcinomas. 15 Study of colon cancer has shown that a mutation in either the APC or the A-catenin gene can result in an atypical accumulation of A-catenin within cells. 15,16 Dysregulation of the Wnt pathway results in the accumulation of A-catenin in the nucleus and cytoplasm and in the transcriptional activation of target genes.…”

“…15 Study of colon cancer has shown that a mutation in either the APC or the A-catenin gene can result in an atypical accumulation of A-catenin within cells. 15,16 Dysregulation of the Wnt pathway results in the accumulation of A-catenin in the nucleus and cytoplasm and in the transcriptional activation of target genes. Aberrant accumulation of A-catenin correlates with tumor histological grade and poor survival.…”

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

“…This indicates that the known intracellular interactions and regulations of MTA proteins in ovarian cancer are probably overlapped by further, yet unidentified, factors that contribute to the expressional regulation of MTA proteins and their downstream targets in ovarian cancer. For example, gene mutation and promoter methylation have been recognized as independent mechanisms of E-cadherin silencing in ovarian cancer [3,37]. The interaction of tumor cells with stroma cells and infiltrating immune cells has to be considered as well.…”