Objectives:To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal cancer (CRC) and its role in carcinogenesis and prognosis.Methods:It was a retrospective study. Archival samples were obtained from Pathology Department at King Fahad Hospital, Madinah, Saudi Arabia, over 11 years’ period (January 2006 to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20 cases of normal colonic mucosa.Results:Cyclooxygenase-2 over-expression was observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of CRC cases. There were no significant correlations between COX-2 over-expression and age, gender, tumor site, or tumor size. However, COX-2 over-expression revealed highly significant correlations with tumor differentiation, lymph node metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that patients with high COX-2 expression had significantly shorter periods of survival. Multivariate analysis by means of the COX-2 regression model revealed that high COX-2 over-expression, AJCC, and Ki67 expression were the only significant independent prognostic indicators.Conclusion:Cyclooxygenase-2 over-expression increases during normal-adenoma-carcinoma sequence, moreover COX-2 over-expression is associated with advanced tumor stage and Ki67 over-expression. These findings suggest a significant role of COX-2 in the carcinogenesis and prognosis of CRC in our study population.

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Background and study aim: Cyclin D1 is a key regulatory protein in the cell cycle and is over-expressed in many tumors, including endometrial, thyroid, urothelial, breast, brain gliomas, and esophageal cancers. The main aim of the present study is to examine the expression pattern of cyclin D1 and its correlation with the different clinicopathological features in patients with colorectal camcer (CRC) from the Madinah region of Saudi Arabia. Patients and methods:The archival tumor blocks were analyzed using immunohistochemistry for Cyclin D1 over-expression in 324 CRC patients diagnosed from January 2006 to December 2017, at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia.Results: Cyclin D1 over-expression was absent in normal mucosa, while 15% cases of adenoma showed its over-expression. In CRC, Cyclin D1 was expressed at high levels in 24.1% of case. No significant correlation was observed between Cyclin D1 over-expression and age, gender, tumor size, type and location. However, Cyclin D1 over-expression exhibited a significant correlation with tumor differentiation (p=0.04), lymph node involvement (p=0.001), lymphovascular invasion (p=0.001), distant metastasis (p=0.006) and AJCC staging (p=0.001). The Kaplan-Meir analysis revealed a shorter period of survival with Cyclin D1 over-expression (p=0.000). The Cox-regression model analysis showed that Cyclin D1 over-expression was an independent prognostic marker in CRC (p=0.000). Conclusion: Cyclin D1 over-expression increases during normal-adenoma-carcinoma sequence. The significant association observed between Cyclin D1 over-expression, advanced tumor stage and short survival period clearly suggest the role of Cyclin D1 in the carcinogenesis and progression of CRC.

Objectives: To evaluate p63 expression pattern in Saudi colorectal cancer (CRC) patients and correlate that with clinicopathological parameters and its role in carcinogenesis and prognosis. Methods: Archival tumor samples were analyzed by immunohistochemistry for p63 expression in 324 consecutive Saudi patients diagnosed with CRC between January 2006 and December 2017 at the Pathology Department of a tertiary care Hospital, Madinah, Saudi Arabia. Results: P63 over-expression was absent in normal mucosa, while 12.5% cases of adenoma showed its over-expression. In CRC, p63 expression was high in 24.1% of cases. There were no significant correlations between p63 expression and gender, tumor location, tumor size, and tumor histologic differentiation. However, high p63 expression revealed a significant correlation with age ( p =0.035), tumor type ( p =0.004), American Joint Committee on Cancer stage ( p =0.046), lymph node metastasis ( p =0.006), lymphovascular invasion ( p =0.006), distant metastasis ( p =0.049) high Ki67 expression ( p =0.000) and K-ras expression ( p =0.002). The Kaplan-Meier analysis revealed a shorter period of survival with p63 over-expression ( p <0.001). The Cox-regression model analysis showed that p63 over-expression was an independent prognostic marker in CRC ( p =0.000). Conclusion: P63 expression increased from normal to adenoma to carcinoma sequence. Moreover, p63 cytoplasmic expression seems to be related to high Ki67 indexing, K-ras expression, advanced tumor stage and poor clinical outcome of CRC. These findings suggest a significant role of cytoplasmic p63 expression in tumor progression and prognosis.