الفهرس 
Colorectal carcinomaOnly 14 pages are availabe for public view
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Abstract
In Egypt, colorectal carcinoma (CRC) has become a significant cause of cancer mortality. A rapid increase in colorectal cancer incidence has been observed where the occurrence was formerly low.
There is current interest in the idea that organ-specific stem cells may provide the origins for cancer development. In the bowel, the mucosal stem cells in the base of the colonic crypts may accumulate mutations and hence lead to tumor development.
Within any cancer, there is only a small subpopulation of cells that have the capacity to generate new primary tumors. These cells are termed cancer stem cells primarily because of their ability to self-renew and regenerate tumor tissue.
Cancer stem cells are similar to normal adult stem cells but with the addition of several features that cause physiologic disarray: angiogenesis, invasion, metastasis and resistance to apoptosis.
The realization that only a minority of cells drive tumorigenesis has important implications for the treatment of cancer. The mainstay of anticancer therapies, apart from surgery, is to target rapidly dividing cells. With the stem cell model for cancer, these therapies would target the transit-amplifying cells and differentiated cells that form more than 99% of the tumor. The cancer stem cells that can initiate new tumors are relatively slow cycling and are therefore less affected by these therapies.
The identification of normal and malignant colorectal stem cells has always been difficult. Only recently, new methods have arisen to aid in their identification and isolation. At this stage, the most important of these has been the identification of surface markers by immunohistochemistry.
The present study was conducted to study the expression of stem cell markers CD133 and Oct 4 and assess their role in colorectal adenocarcinoma.
The current study included 70 cases of colorectal carcinoma performed by surgical resection. The specimens were obtained from the pathology department of Ain Shams University Hospitals in the years 2010 and 2011.
All cases were studied along the following lines:
(I) Demographic and clinical studies: by reviewing the files of the patients for age, gender, tumor site, size and recurrence.
(II) Histopathologic study: by reexamining the Hx&E slides for:
- Confirmation of the diagnosis of CRC and determination of the type of the tumor.
- Adenocarcinoma cases were graded into I, II & III and all cases were staged according to modified Dukes’ classification and TNM staging system.
- Tumors were examined for lymphovascular and perineural invasion.
(III) Immunohistochemical study:
- Immunohistochemical examination of CRC cases for CD133 and Oct4 proteins.
Finally, correlation of the expression of CD133 and Oct4 proteins with the different clinico-pathological features of CRC as regards; age, gender, tumor site, tumor size, type, grade, modified Dukes’ stage, TNM stage, lymphovascular & perineural invasion and tumor recurrence.
The results revealed high expression of CD133 protein in 62 cases (88.6%) of CRC cases whereas; the high expression of Oct4 protein in 27 cases (38.6%). On the other hand; the low expression of CD133 protein was detected in 8 cases (11.4%) while the low expression of Oct4 was in 43 cases (61.4%). There was a statistically significant difference between the expression of CD133 and Oct4 proteins among the studied cases (P = 0.033).
Concerning the correlation of the expression of CD133 and Oct4 proteins with the clinicopathological features of CRC, the present study revealed a statistically significant relation between CD133 expression and tumor site as the high expression was detected more in left colon tumors. There was a significant relationship between Oct4 expression and tumor type as Oct4 low expression was associated with adeno-carcinoma cases and all cases of signet ring carcinoma had high Oct4 expression. Also, there was a significant relation between Oct4 expression and both modified Dukes’ stage and M stage of the tumor. Low Oct4 expression was associated with modified Dukes’ stage B cases and all stage D cases had high Oct4 expression. All cases of distant metastasis showed high Oct4 expression.
In conclusion, our study found no significant relationship between CD133 expression and the prognostic clinicopathological parameters. Moreover, CD133 expression was detected in normal, dysplastic colonic mucosa and tumor tissues.
While the complete absence of Oct4 expression in normal colonic mucosa and its expression in dysplastic mucosa and in carcinoma cases may suggest the oncogenic role of Oct4 in colorectal carcinogenesis. Moreover, embryonic stem cell marker Oct4 expression may have prognostic significance in patients with colorectal carcinoma as lower expression was significantly associated with modified Dukes’ stage B and absent distant metastasis while higher expression was associated with modified Dukes’ stage D and presence of distant metastasis.