Albasri Abdulkader Mohammed, Elkablawy Mohammed Aboulmatty, Ansari Irfan Altaf, Alhujaily Ahmed Safar
Department of Pathology, Taibah University, Universities Road, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia. Email:
Department of Pathology, Menofia University, Menofia, Egypt.
Asian Pac J Cancer Prev. 2019 Aug 1;20(8):2471-2476. doi: 10.31557/APJCP.2019.20.8.2471.
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.
细胞周期蛋白D1是细胞周期中的关键调节蛋白,在包括子宫内膜癌、甲状腺癌、尿路上皮癌、乳腺癌、脑胶质瘤和食管癌在内的多种肿瘤中过度表达。本研究的主要目的是检测沙特阿拉伯麦地那地区结直肠癌(CRC)患者中细胞周期蛋白D1的表达模式及其与不同临床病理特征的相关性。
对2006年1月至2017年12月在沙特阿拉伯麦地那法赫德国王医院病理科诊断的324例CRC患者的存档肿瘤组织块进行免疫组织化学分析,以检测细胞周期蛋白D1的过度表达情况。
正常黏膜中未检测到细胞周期蛋白D1的过度表达,而15%的腺瘤病例显示其过度表达。在CRC中,24.1%的病例细胞周期蛋白D1呈高水平表达。细胞周期蛋白D1的过度表达与年龄、性别、肿瘤大小、类型和位置之间未观察到显著相关性。然而,细胞周期蛋白D1的过度表达与肿瘤分化(p=0.04)、淋巴结受累(p=0.001)、淋巴管浸润(p=0.001)、远处转移(p=0.006)和美国癌症联合委员会(AJCC)分期(p=0.001)显著相关。Kaplan-Meir分析显示,细胞周期蛋白D1过度表达的患者生存期较短(p=0.000)。Cox回归模型分析表明,细胞周期蛋白D1的过度表达是CRC的独立预后标志物(p=0.000)。
在正常-腺瘤-癌序列过程中,细胞周期蛋白D1的过度表达增加。细胞周期蛋白D1的过度表达、肿瘤晚期和生存期短之间的显著关联清楚地表明了细胞周期蛋白D1在CRC发生和发展中的作用。