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

Abstract

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