Prognostic Significance of Cyclin D1 Over-expression in Colorectal Cancer: An Experience from Madinah, Saudi Arabia

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.