الفهرس 
CytokeratinOnly 14 pages are availabe for public view
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Abstract
Colorectal carcinoma (CRC) is considered the second commonest cause of cancer worldwide. It accounts for 783,000 new cases per year (9.7% of all cancer cases worldwide), and 437,000 cases of death (8.4%).The incidence of CRC is not much different in males and females (ratio 1.05:1.00). CRC ranks third in frequency in men (after prostate and lung cancer) and third in women (after breast and lung cancer). The cytokeratin (CK) family is a highly complex multigene family of polypeptides, the molecular weight of which ranges from 40 to 68 KDa. The clinical usefulness of cytokeratin tumor markers is well established for monitoring patients with epithelial cell carcinomas. The cytokeratins reflect tumor cell activity. Thus, by following patients with repeated assays of a cytokeratin marker in combination with a marker that reflects tumor burden, the oncologist can obtain critical information about tumor growth activity. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. VEGF family and its receptors play a pivotal role in normal and pathologic angiogenesis. Over expression of VEGF is associated with poor prognosis and reduced overall survival in a wide variety of human cancers. This study was carried on 50 subjects; 40 patients with histologically confirmed colorectal carcinoma undergoing elective surgery at Gastroenterology Center, Mansoura University Hospital (18 males and 22 females) with their ages ranged from 18-65 years and 10 healthy individuals (4 males and 6 females) matched for age and sex. Patients were subjected to the following: Clinical, endoscopic, radiological, histopathological evaluation. Routine investigations including, serum albumin, bilirubin, ALT, AST, creatinine, CEA, CA19-9, CBC and specific investigations in form of study of CK20 &VEGF expression by real time quantitative RT-PCR were done for both patients and controls. This study showed that: Ι- Statistical significant high levels of CEA, CA19-9, CK20 and VEGF in CRC patients when compared with controls. П- Serum level of CEA and CA19-9 in CRC patients showed: Statistical significant increase in the serum CEA level in CRC patients stage B versus stage A, and CRC patients stage C versus stage A. Statistical significant increase in the serum CEA and CA19-9 levels between all CRC patients’ grades. Statistical significant increase in the serum CEA level in CRC patients with L.N metastasis versus CRC patients without L.N metastasis. Statistical insignificant difference in the serum CEA level in CRC patients stage C versus stage B, also between serum CA19-9 level and all CRC stages or L.N metastasis. Ш- CK20 expression in CRC patients showed: Statistical significant increase in the expression of CK20 between all CRC stages versus controls. Statistical significant increase in the expression of CK20 in CRC patients stage C versus stage A, and CRC patients stage C versus stage B. Highly significant increase in the expression of CK20 in CRC patients with L.N metastasis versus CRC patients without L.N metastasis. Statistical insignificant difference in the CK20 expression between CRC stage B versus stage A and between CRC grades. ΙV- VEGF expression in CRC patients showed: Statistical significant increase in the expression of VEGF between all CRC stages versus controls. Statistical significant increase in the expression of VEGF in CRC patients stage C versus stage A, and CRC patients stage C versus stage B. Statistical significant increase in the expression of VEGF in CRC patients’ grade П versus grade Ι & grade Ш versus grade Ι. Highly significant increase in the expression of VEGF in CRC patients with L.N metastasis versus CRC patients without L.N metastasis. Statistical insignificant difference in VEGF expression between CRC stage B versus stage A and between grade Ш versus grade П. V- Correlation between studied markers in CRC patients showed: There were statistical positive correlation between CK20 and VEGF expressions, and also between these markers and CEA level. There was statistical positive correlation between VEGF expression, and CA19-9 level. There was statistical insignificant correlation between CK20 expression and CA19-9 level. Conclusions: From this study it could be concluded that: Quantitative RT-PCR detection for CK20 and VEGF expression in peripheral blood of CRC patients may have a clinical significance in monitoring early stage hematogenous spreading that may further develop into metastasis or recurrence. CK20 expression was highly increased in CRC patients with positive correlation between its expression and advancing Dukes’ stages, L.N metastasis, CEA level. VEGF expression was highly increased in CRC patients with positive correlation between its expression and advancing Dukes’ stages, tumor grades, L.N metastasis, CEA and CA19-9 levels. This finding offers the use of anti-VEGF monoclonal antibodies as a potential immunotherapeutic agent for treatment of colorectal carcinoma. CK20 and VEGF expression are promising complementary molecular markers for CRC progression and metastasis. Recommendations: The lack of a standardized method to detect disseminated tumor cells is a clear barrier to the clinical implementation of CTC detection. As a result, there is an important need to continue further studies on CK20 and VEGF to involve standardized techniques with an ability to discriminate expression levels in a quantitative RT-PCR on wide scale of patients and follow up their expression postoperatively. More attention should be given to the significance of quantitative detection of CK20 and VEGF as early indicator of high-risk patients. Their detection may help in monitoring the occurrence of metastasis, recurrence, and therapeutic outcome