细胞周期调控因子在胃癌组织中的表达及意义

背景与目的细胞周期调控异常与细胞过度增殖及肿瘤发生密切相关,而细胞周期调控因子与胃癌的关系尚未明确。本研究目的是探讨细胞周期调控因子P16INK4、CyclinD1、P21WAF1、P53在胃癌组织中的表达及意义。方法运用免疫组织化学SP法检测53例胃癌及癌旁组织中细胞周期调控因子P16INK4、CyclinD1、P21WAF1、P53的表达。采用多变量Cox回归模型对影响预后的因素进行分析。结果P53蛋白在胃癌组织中的阳性率为60.4%,显著高于癌旁组织(0%)(P<0.01);P53蛋白表达在粘液癌(0%)与高分化腺癌(65.4%)和低分化腺癌(68.2%)间有显著性差异(P<0.01)。CyclinD1蛋白在胃癌组织中的过表达率为69.8%,显著高于癌旁组织(5.7%)(P<0.01)。P16INK4蛋白在胃癌组织中的阳性率为60.3%,显著低于癌旁组织(88.6%)(P<0.05)。P21WAF1蛋白在胃癌组织中的阳性率为26.4%,显著低于癌旁组织(56.6%)(P<0.01)。P16INK4表达与胃癌浸润深度及淋巴结转移相关(分别为P<0.05,P<0.01)。多因素Cox回归分析表明,淋巴结转移、P16INK4为独立预后因素。结论P16INK4蛋白、P21WAF1蛋白低表达和CyclinD1蛋白、P53过度表达与胃癌发生发展有关;P16INK4蛋白的低表达与胃癌浸润、转移及预后有一定关系。

Expression and significance of cell cycle regulators in gastric carcinoma

BACKGROUND & OBJECTIVE: Abnormality of cell cycle regulation is an important cause of cell over-proliferation and oncogenesis. But the relationship between cell cycle regulators and gastric carcinoma is uncertain. This study was to investigate the expression and significance of cell cycle regulators, including P16INK4, Cyclin D1, P21WAF1, and P53, in gastric carcinoma. METHODS: The expressions of P16INK4, Cyclin D1, P21WAF1, and P53 in 53 specimens of gastric carcinoma were observed by SP immunohistochemistry. Multivariate Cox regression was used to analyze factors affecting prognosis. RESULTS: Positive rate of P53 in gastric carcinoma was higher than that in adjacent tissues (60.4% vs. 0, P < 0.01); those in well, and poorly differentiated adenocarcinoma were significantly higher than that in mucoid carcinoma (65.4%, and 68.2% vs. 0, P < 0.01). Over-expression rate of Cyclin D1 in gastric carcinoma was higher than that in adjacent tissues (69.8% vs. 5.7%, P < 0.01). Positive rate of P16INK4 in gastric carcinoma was lower than that in adjacent tissues (60.3% vs. 88.6%, P < 0.05). Positive rate of P21WAF1 in gastric carcinoma was lower than that in adjacent tissues (26.4% vs. 56.6%, P < 0.01). Positive rate of P16INK4 was significantly related with the depth of tumor invasion (P < 0.05), and lymph node metastasis (P < 0.01). Multivariate Cox regression analysis indicated that lymph node metastasis and the expression of P16INK4 were independent prognostic factors of gastric carcinoma. CONCLUSIONS: Down-regulation of P16INK4 and P21WAF1, and over-expression of Cyclin D1 and P53 are significantly related to genesis and progression of gastric carcinoma. Down-regulation of P16INK4 may be correlated to infiltration, metastasis, and prognosis of gastric carcinoma.