الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Summary and Conclusion
CRC is the third most common cancer worldwide after lung and breast cancers . CRC is a major public health problem because approximately 50% of CRC cases develop metastasis.
Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells are thought to be responsible for tumor initiation, dissemination and treatment failure. Therefore, we hypothesized that CRCSC markers will identify a group of patients at high risk for progression.
EPCAM, a 40 kDa glycoprotein, functions as an epithelial cell adhesion molecule. Its expression has been reported as localized to the epithelium along the basolateral surface of the majority of GIT mucosa. It is expressed in 85% of colorectal carcinomas and is one of the earliest tumor markers to appear that is involved in signal transduction, regeneration of tissue and other biological functions.
ALDH1B1 is a relatively unexplored member of the ALDH superfamily. High ALDH1B1 expression was observed throughout the cells of human colon adenocarcinomas.
The present study included 50 specimens of colorectal carcinomas, received in the Pathology Laboratory of Sohag University Hospital from the Department of Surgery through the period from January 2015 to December 2017.
The mean age of the studied patients was 56.2 years. The tumor size was ≤5 cm in 21/50 (42%) cases and >5 cm in 29/50 (58%) cases.
The H & E stained sections of the 50 cases were evaluated and they revealed that there were 34/50 (68%) cases of conventional adenocarcinoma, 12/50 (24%) cases of mucinous carcinoma, 4/50 (8%) cases of signet ring carcinoma. The colorectal carcinomas were graded in accordance with the WHO grading criteria into: grade I; 9/50 (18%), grade II; 22/50 (44%) and grade III; 19/50 (38%). Regional lymph node metastasis was positive in 27/50 (54%) cases. LVI was observed in 8/50 (16%) cases.
Sections from the 50 cases were immunostained with EPCAM and ALDH1B1 to detect their expressions and they revealed that EPCAM was expressed in all cases (100%); strongly expressed in 29/50 (58%) of cases of colorectal carcinoma, moderately expressed in 18/50 (36%) of cases and weekly expressed in 3/50(6%) of cases. Most of the cases strongly expressing EPCAM 24/29 (82.75%) were conventional adenocarcinoma.
Current study showed that decreased EPCAM expression was positively correlated with tumor grade of differentiation, lymph node status, surgical resection margin and signet ring histology. However, no correlation was found between EPCAM expression and the age, sex, tumor size, tumor depth of invasion and LVI.
ALDH1B1 was expressed in all cases (100%) of colorectal carcinoma. It was strongly expressed in 12/50 (24%), moderately expressed in 31/50 (62%), and weakly expressed in 7/50 (14%) cases. Our study showed that ALDH1B1 was positively correlated with tumor grade, lymph node status and tumor size. However, statistical evaluation of ALDH1B1 expression according to age, sex, tumor depth of invasion, histologic type and LVI showed no significance.
There was no significant correlation between EPCAM and ALDH1B1 expression in colorectal carcinoma in this study.
Conclusion
• The present study suggests that down-regulation of EPCAM expression with reduced membranous and appearance of cytoplasmic expression is correlated with tumor progression, increasing grade of colorectal carcinoma, LN metastasis and poor prognosis of CRC.
• These findings indicate that EPCAM is involved in the transformation and progression of CRC and that its low-expression is a significant unfavorable prognostic factor and may serve as a predictor for patient outcomes.
• The up-regulation of ALDH1B1 with increasing grade of colorectal carcinoma and/or presence of LN metastases indicates that ALDH1B1 might play a role in carcinogenesis and tumor progression.
• Our results suggest that overexpression of ALDH1B1 may represent unfavorable prognostic factor in CRC.
• These findings may lend themselves to a new strategy of individualized adjuvant therapy selection and post-treatment surveillance aimed at identifying patients with the highest likelihood of disease recurrence or progression.
Recommendations
1. Studying the expression of EPCAM and ALDH1B1 on a large number of cases and different varieties of CRC.
2. Prospective studies properly powered based on this study should be undertaken to determine the significance of these early findings; follow up of patients and getting enough information about distant metastasis to emphasize the correlation between EPCAM and ALDH1B1 expression and the patient survival and disease outcome.
3. Studying the change in expression of EPCAM and ALDH1B1 in correlation with other CRCSC markers (e.g CD29, CD44, CD166 and CD133) to clarify their role in CRC tumorgenesis.