Jaafar Sadeq Makki (2014) Expression distribution of cancer stem cell, epithelial to mesenchymal transition and telomerase activity in breast cancer, and their association with clinicopathological characteristic. Doctoral thesis, Universiti Malaysia Sabah.
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Abstract
Three novel concepts have been emerged in breast cancer biology: the role of cancer stem cells (CSC) in tumor initiation, and the involvement of an epithelial to mesenchymal transition (EMT) in the invasiveness and metastasis of cancer cells, along with the telomerase role in keeping the CSC immortal, and avoiding senescence. CSC are a small subpopulation of cells within tumors that initiate the tumor, telomerase is the intracellular enzyme responsible for the elongation of chromosomal telomer during each cell division, while EMT is the loss of epithelial differentiation and gained the mesenchymal phenotype. The objective of this study is to analyse and determine the prevalence, and prognosticimportance of CSC, Telomerase activity, and epithelial to mesenchymal transition, in primary and metastatic breast carcinoma, and associationbetween each other. A total of 167 surgically resected primary invasive breast carcinomas, and 63 metastatic lymph node lesionwere analysed forimmunohistochemical localization of the CD44+CD24-lowbreast CSC markers, and EMT markers,vimentin and Ecadherin, by double staining IHC technique, as well as telomerase activity in formaline fixed paraffin embedded tissue, the results was validated by double staining immunoflourecent and flow cytometry techniques. The results showed CSC with CD44+CD24-low phenotype was significantly increased in node-positive tumours (p<0.0001), and in high grade tumors (p<0.0001), so CSC is independent, negative prognostic factor, its presence indicate poor prognosis, there was considerable high incidence of these cells in metastatic lymph node lesion compared to primary tumor (p-0.000), CD44+CD24- low phenotypic cells was more prevalent and in significant number in ductal carcinoma insitu (DCIS) comparing to its invasive counterpart (p- 0.001). There was no significant correlation observed in between telomerase activity and clinicopathologicalbreast cancer parameters,but there was considerable high incidence of telomerase expression in metastatic lymph node lesion. EMT was more expressed in special subtypes of invasive carcinoma comparing to IDC (NOS). The incidence of EMT was more in triple negative tumor. EMT expression was more prevalence in DCIS lesion relative to its invasive component (p-value 0.000),and there was considerable high number of tumor cells with EMT expression in metastatic lymph node lesion (p-0.001).The occurrence of EMT phenomena was usually accompanied by the co-existence of CSC of CD44+CD24-low phenotype. There was no association between the existence of CSC and detection of telomerase activity in tumor cells. Increase number of both CSC of CD44+CD24-lowphenotype and cells underwent EMT in DCIS lesion might be an initial step in the stromal invasion and propagation of breast cancer, and induction of EMT in the breast tumor associated with high prevalence of CSC, promoting tumorinvasiveness and metastasis. EMT occurrence is always co-existence with CSC subsistence, suggesting that EMT phenotype induced by different factors are rich sources for CSC, which raise the possibility of biological similarities between CSC, and EMT-phenotypic cells. Finally, we can conclude that the currently used detection methods for breast CSC and EMT are not enough to identify all subtypes of these tumor cell. The clinical relevance on prognosis and therapy response has to be further evaluated in a prospective trial.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Keyword: | Cancer stem cells, Epithelial-to-mesenchymal transition, Telomerase activity, Breast cancer, Clinicopathological characteristics, Tumor invasiveness, Metastasis |
| Subjects: | R Medicine > RC Internal medicine > RC31-1245 Internal medicine > RC254-282 Neoplasms. Tumors. Oncology Including cancer and carcinogens |
| Department: | FACULTY > Faculty of Medicine and Health Sciences |
| Depositing User: | DG MASNIAH AHMAD - |
| Date Deposited: | 07 Apr 2025 11:38 |
| Last Modified: | 07 Apr 2025 11:38 |
| URI: | https://eprints.ums.edu.my/id/eprint/43364 |
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