الفهرس 
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Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide after lung and breast cancers. In Egypt, there is an increasing incidence of CRC, especially among patients ≤ 40 years of age. CRC in Egypt is the fifth following urinary bladder, liver, non Hodgkin lymphoma and lung carcinoma. The incidence according to results of the National Population-Based Cancer Registry Program, Egypt was 3.57%.
Metastases are the end result of tumor progression and are the most common cause of death in cancer patients. The genetic bases for metastasis are beginning to be outlined. Altered functions of several genes, that are key players in embryonic development, are related to some steps in oncogenesis, such as epithelial-mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their polarity and are converted to mesenchymal phenotypes. Thus, EMT represents a cellular program that confers on neoplastic epithelial cells the biological traits needed to accomplish most of the steps of the invasion–metastasis cascade. EMT is controlled by a group of transcriptional repressors (Twist, Zeb-1, Zeb-2, Snail, and Slug) that recruit histone deacetylases to E-box elements that are located within the E-cadherin promoter and a variety of other genes. This study focused on Twist because it is considered as one of the master regulators of EMT through indirect (Twist) suppression of E-Cadherin (CDH1). It is considered to be important for metastasis in
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several cancer types. Also, the aberrant expression of Twist is frequently reported in CRC. The Twist proteins are embryonic transcription factors that play key roles in embryonic development. While they remain largely undetectable in healthy adult tissues, both Twist 1 and Twist 2 genes are frequently reactivated in a wide array of human cancers, where they invariably correlate with more aggressive, invasive and metastatic lesions.
It is also possible that Twist, acting as a bHLH transcription factor, binds directly to the E-boxes on the E-cadherin promoter to suppress its transcription. In addition to silencing E-cadherin transcription, it was also found that Twist induces the expression of mesenchymal markers, such as fibronectin and N-cadherin, during an EMT
This work was planned to evaluate the immunohistochemical expression of Twist, E-cadherin and vimentin to explore the EMT mechanism in colorectal cancer (CRC) of Egyptien patient.
This study was carried out on 93 specimens; 10 specimens from normal colonic mucosa, 8 colonic adenoma, 49 CRC cases and 26 metastatic CRC specimens (all are metastatic from our primary CRC case).
This study evaluated the positivity and negativity of Twist as well as intensity and extent of both cytoplasmic staining as well as N/C staining of Twist. An overall staining score of 0-5 and 6-7 were regarded as low and high Twist expression, respectively. Similarly, this study evaluated the intensity and extent of membranous E-cadherin expression. An
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overall staining score of 0-5 and 6-7 were regarded as low and high Twist expression, respectively. In addition, cytoplasmic staining for Vimentin was evaluated.
Data were collected, tabulated and statistically analyzed using a personal computer with ”Statistical Package for the Social Sciences (SPSS) version 16” program.
The ten specimens (100%) of normal non neoplastic colonic epithelium showed no nuclear Twist immunoreactivity. Low cytoplasmic immunostaining (score 0-5) was detected in 10/10 (100%) of normal colonic mucosa cases. All normal colonic mucosa specimens showed high E-cadherin immunostaining, while they all were negative for vimentin.
All the adjacent non tumorous mucosa that appeared in 17 CRC cases with high Twist immunostaining (score 6-7) showed high Twist cytoplasmic expression. No nuclear Twist expression was detected in any of them. All the adjacent non tumorous mucosa showed preserved high E-cadherin immunostaining, while they all were negative for vimentin.
All the studied adenoma cases (100%) were negative for nuclear expression of Twist. Six out of eight (75%) studied adenoma cases showed high cytoplasmic expression of Twist.
Expression of twist in the adjacent tumor stroma including background lymphocytes and fibroblasts was evaluated in the adjacent non tumorous mucosa, adenoma and CRC cases. Nucleo-cytoplasmic Twist positivity was found in adjacent tumor stroma and background lymphocytes comparable to its expression in adjacent tissues.
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There was no statistical significant association between cytoplasmic expression of Twist and clinicopathological features of colorectal adenoma.
Fifteen out of forty nine cases of CRC (30.6%) showed low cytoplasmic expression of Twist. Thirty four out of forty nine cases of CRC (69.4%) showed high cytoplasmic expression of Twist.
There was no statistical significant association between cytoplasmic expression of Twist in CRC and the available clinicopathological data using low and high scoring system as well as using positive and negative evaluation method. There was no signification association between apoptotic index and cytoplasmic expression of Twist. However there was slight decrease in apoptotic index with high cytoplasmic expression of twist.
Both colorectal adenoma and CRC cases showed much higher cytoplasmic expression of Twist than normal colorectal mucosa. There was no statistical significant association between adenoma and CRC cases regarding cytoplasmic Twist expression.
There was highly significant inverse association between cytoplasmic expression of Twist and expression of E-cadherin (P=0.007). Thirty four out of thirty four (100%) of cases showed high cytoplasmic expression of Twist were associated with low expression of E-cadherin.
There was highly significant direct relationship between cytoplasmic expression of Twist and vimentin (P=0.008). Fifteen out of fifteen (100%) cases with low cytoplasmic expression of Twist were associated with negative vimentin.