الفهرس 
2.Review of literatureOnly 14 pages are availabe for public view
 |  | from | 155 |  |  |
| | | from | 155 | | |
Abstract
Breast cancer cells invade and generate metastasis through either lymphatic or blood vessels systems. Interactions between luminal epithelial cells and their surrounding environment are present during the normal development and function of the mammary gland. Alterations in these interactions can induce abnormal intracellular signaling pathways that might affect development and progression of breast tumors.
Transcription factors are gaining more attention in the field, since they can be highly effective in treating particular malignancies related to hormone receptors. Also they have controversial and contradictory roles in the field of oncology, during cell proliferation, migration, invasion, tumor metastasis and suppression.
Zinc finger proteins C2H2 family like ZEB-1 protein was found to impact the adhesions between cells thus affecting their morphology which contributes to cancer spread. B-cell Lymphoma 11A gene is expressed to a zinc finger protein C2H2 that has a role in lymphoid development and is closely related to B-cell proliferation and differentiation and its aberrant expression is associated with T-cell malignancies.
Thus, the current study was designed to investigate the levels
Summary and Conclusion
109
of E-cadherin, SOX11 and BCL11A in recently diagnosed pre-treated breast cancer females with no distant metastasis. In addition to, benign female cases with fibroadeoma and apparently healthy control females.
In order to fulfill this objective our study was conducted on 84 female subjects divided into the following three groups;
group (I): The control group:
The first group (n = 19) included healthy subjects.
group (II): Patients with fibroadenoma or fibrocystic changes:
The second group (n = 20) included benign subjects.
group (III): Patients with BC:
The third group (n = 45) included pre-treated malignant subjects with no distant metastasis.
Biochemical markers for liver functions and kidney functions such as; ALT, AST, urea and creatinine were measured. Also, serum levels of CEA, CA15.3 and E-cadherin, SOX11 and BCL11A were assessed by ELISA. Then the correlations between these parameters were examined statistically to gain more insight into our results.
Summary and Conclusion
110
Results of the current study can be summarized as follows:
1. Significantly elevated levels of CEA and CA15.3 were observed in the cancerous subjects.
2. Serum E-cadherin levels were significantly higher in cancerous subjects.
3. Lobular carcinomas revealed significantly higher E-cadherin levels than ductal carcinomas.
4. Serum SOX11 levels were significantly low in cancerous subjects than non-cancerous and associated with tumor stages.
5. Serum BCL11A levels were significantly low in cancerous subjects than non-cancerous subjects. However, not associated with any of the tumor clinic-pathological characteristics.
6. Interestingly, the sensitivity and the specificity of the combined ROC curve for CA15.3 and SOX11 were higher than using CA15.3 alone.
7. Significant elevated levels of E-cadherin in Luminal A sub-type than TNBC while the TNBC sub-type showed the highest levels of BCL11A.
Summary and Conclusion
111
8. On conducting spearman correlations it was found that serum SOX11 was negatively correlating with CA15.3.
9. Spearman correlations revealed that Serum SOX11 was positively correlating with BCL11A.
In conclusion, the current study provides evidence for:
1. E-cadherin mediates tumor cell-cell adhesion. The partial or complete loss of E-cadherin expression correlates with poor survival and prognosis in BC patients.
2. Higher serum E-cadherin levels might indicate the lack of cohesiveness and adhesions that form the integrity within the cells. Lobular carcinomas are associated with a more aggressive, migratory and mesenchymal phenotype than ductal carcinomas that can be justified due the loss of E-cadherin in their cell membrane and junctions.
3. Sex determining region y- box serum levels were associated with tumor stages, as higher levels were observed in earlier stages suggesting that SOX11 silencing increased the proliferation and significantly increased the ability of colony formation, also higher levels slow down the tumor aggressiveness through inhibiting the Wnt pathway as agreed in published literature.
Summary and Conclusion
112
4. BCL11A has no role in BC sub-types but further research should be conducted to exclude TNBC from this conclusion.
5. The diagnostic utility and the interplay between studied E-cadherin, and SOX11 together with the well-established markers like CA15.3 in BC can aid greatly in raising the sensitivity and specificity for these tests than solely using one parameter.
6. A mechanism of down regulation to E-cadherin expression might be present in TNBC sub-type which can contribute to its aggressiveness and the rapidly spreading behavior.
7. The negative correlation between SOX11 and CA15.3 indicate a potential crosstalk occurring between these markers in the pathogenesis of the disease and stages.
8. The positive correlation between SOX11 and BCL11A is probably due to sharing of some common pathways during lymphoid development.
Recommendations
113
7. Recommendations
1. Explore the mechanism involved in inhibition of SOX11in cancerous subjects and its link with the apoptosis pathways or with other tumor suppressor’s proteins as p53.
2. Study the relation between BCL11A and TNBC sub-type specifically.
3. Explore the feasibility of using the E-cadherin as a routine test as a diagnostic aid marker in EMT malignancies.
4. Study the effect of epigenetic modifications in BC patients on these markers.
References
114
8