大肠癌p27蛋白表达与DNA倍体分析的研究

Relationship between Expression of p27 and DNA Ploidy in Colorectal Carcinoma

背景与目的:细胞周期调控的改变存在于绝大多数肿瘤中,因此可以认为肿瘤是一类细胞周期疾病。p27蛋白是细胞周期负性调控因子的主要成员,同时也是肿瘤的重要预后因子。p27蛋白表达下降及亚细胞定位改变在大肠癌发展中的意义尚不清楚。大肠癌中p27蛋白表达与DNA倍体关系尚未见报道。本实验研究大肠癌p27蛋白表达与临床病理特征及DNA倍体分析的关系。方法:应用免疫组化方法检测p27蛋白在40例大肠癌中的表达水平,同时应用病理图像DNA测量系统对癌组织进行倍体分析。结果:p27蛋白在大肠癌中的高表达率为62.5%(25/40),低表达率为37.5%(15/40),p27蛋白低表达与大肠癌分化程度低显著相关(P<0.05)。除胞核着色外,32.5%(13/40)的大肠癌出现胞浆免疫阳性反应。p27蛋白胞浆表达与Dukes分期晚(P<0.01)、易发生淋巴结转移显著相关(P<0.05)。p27蛋白低表达组DNA多倍体细胞检出率(22.2±11.3)%明显高于p27蛋白高表达组犤(8.0±7.7)%,P<0.001犦。结论:p27蛋白表达的下降及亚细胞定位改变促进大肠癌的发展;抑制DNA多倍体形成可能是p27蛋白的抑癌机理之一。

Background & Objective: Cell cycle regulation changes in most of tumors. We can regard tumors as a kind of cell cycle diseases. p27 protein is a main negative cell cycle regulator, meantime it is an important prognosis factor of tumors. The significance of reduced expression and altered sbucelluar localization of p27 protein is unclear in progression of colorectal carcinoma. The relevance of p27 protein and DNA ploidy hasnt been reported in colorectal carcinoma. The study was designed to investigate the relationship between the expression of p27 protein and clinicopathological features, DNA ploidy in colorectal carcinoma. Method: The expression of p27 was observed in 40 colorectal cancer cases using immunohistochemical technique, and DNA content of cancer cells was analyzed using DNA imaging analysis system. Results: The high p27 expression rate was 62.5%(25/40), while low expression rate was 37.5%(15/40). Low p27 expression was significantly associated with low tumor grade.(P< 0.05). In addition to nuclear staining, 32.5%(13/40) of the carcinoma displayed p27 positive immunoreactivity in cytoplasm. Cytoplasmic localization of p27 was association with late Dukes stage(P< 0.01)and high incidence of lymph node metastases(P< 0.05) . The detective rate of polyploidy cell in the patients with p27 lower expression (22.2±11.3%) was significantly higher than that with p27 higher expression (8.0±7.7%, P< 0.001). Conclusion: Reduced expression and altered subcelluar localization of p27 play a role in progression of colorectal carcinoma; one suppression tumor mechanism of p27 might be to prevent the acquisition of polyploid DNA content in colorectal carcinoma cells.