الفهرس 
Introduction
Epidemiology and risk factors of colorectal carcinomaOnly 14 pages are availabe for public view
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Abstract
CRC incidence and mortality rates vary markedly around the world. Globally, CRC is the third most commonly diagnosed cancer in males and the second in females, with 1.4 million new cases and almost 694,000 deaths estimated in 2012 and 1.65 million new cases and almost 835,000 deaths in 2015. It was detected that introduction of new cytotoxic and targeted agents for patients with metastatic CRC has improved overall survival rates (OS), with expected median survival in excess of 20 months. The current treatment regemin consists of 5-FU based chemotherapy with either oxaliplatin (FOLFOX) or irinotecan. It is important to find biomarkers that would affect the response to these cytotoxic drugs. This may enable us to select the patient who would benefit from these cytotoxic agents. In this work, we studied the role of excision repair cross-complementation group 1 (ERCC1) and Thymidylate synthetase (TS) as biomarkers that can predict response of CRC patients to oxaliplatin and 5-Flurouracil. This study was conducted on 51 cases of colorectal carcinoma have different histological grade and stage. Histological examination was performed to determine the histological grade, stage and the presence or absence of lymphovascular invasion. Regarding Immunohistochemical expression of ERCC-1 and TS in the tumor tissue, the results were evaluated by immunohistochemical scores. Statistical analysis was done and the results were tabulated. The current study identified that there was a statistically significant association between high ERCC-1 immunoexpression and occurance of local recurrence of the tumor and secondary metastasis after receiving chemotherapy (p=0.027 and 0.008 respectively). As well it was detected that high TS immunoexpression was statistically significantly associated with presence of distant metastasis, occurance of local recurrence of the tumor and secondary metastasis after receiving chemotherapy (0.001, 0.019 and 0.011 respectively). In our results, expression levels of ERCC1 and TS were positive significantly correlated (Pearson r=0.340 and p=0.015). As regard DFS, There was statistically significant association between DFS and TS immunoexpression (7 vs. 20 months; P = 0.010). Regarding Univariate analysis of prognostic factors affecting OS, DFS and PFS rates, it was detected that the only prognostic factor affecting OS was gender of the patients as higher OS rate was detected in female patients (p=0.040). According to our results DFS was affected by histological type and grade, longer DFS was associated with well differentiated adenocarcinoma (p=0.038). In our study, PFS has been shorter with deeper tumor invasion and presence of distant metastasis. (p=0.001 and 0.022 respectively). We detected that deep tumor invasion, presence of distant metastasis, presence of lymph node invasion and high Dukes classification are significantly associated with early post operative treatment failure (p=0.001, 0.000, 0.041 and 0.015) respectively. Finally, we detected also that high ERCC-1 and high TS immunoexpression were significantly statistically associated with early postoperative treatment failure. (p=0.020 and 0.000) respectively. In conclusion, take togeather, our findings and published data on the two studied biomarkers we can say that: ERCC-1 and TS immunoexpression in colorectal carcinoma patients could be used as a predictive factor for early postoperative treatment failure. TS expression is a predictive factor for distant metastasis at presentation, local recurrence and secondary metastasis after receiving 5-FU. ERCC1 is a predictive factor for local recurrence and secondary metastasis after receiving oxaliplatin. Both ERCC-1 and TS are correlated together. In addition to ERCC-1 and TS, all of the following can be used as predictive factors for early post operative treatment failue; deep tumor invasion, presence of distant metastasis, presence of lymph node invasion and high Dukes classification. Patient’s gender can be used as a prognostic factor for OS rate, while histological type and grade can be used as a prognostic factor for DFS rate, on other hand PFS rate affected by deep tumor invasion and distant metastasis so those 2 factors can be used in prognosis. All these preliminary data require more in-depth studies such as, performance on a large number of cases with different colorectal carcinoma types and grades to improve the statistical power and reduce the statistical bias and analysis of other molecules interacting with both ERCC-1 and TS immunoexpression. We recommend also to study other variables related to colorectal carcinoma as mutation status of MSI, RAS, TP53 and BRAF as prognostic and predictive factors regarding its effect on DFS, PFS, OS and early post operative treatment failure and their relation to ERCC-1 and TS IHC expression.