子宫内膜增生及癌变组织中增殖细胞核抗原与p16和p53基因表达的相关性研究

Correlation of proliferation cell nuclear antigen,p16 and p53 gene expression in endometrial hyperplasia and carcinoma

目的探讨增殖细胞核抗原（PCNA）及基因p16、p53在单纯性子宫内膜增生（ESH）、子宫内膜不典型增生（EAH）和子宫内膜癌（EC）组织中表达情况。方法应用免疫组化法分别对26例EC、28例EAH、24例ESH组织进行PCNA和p16、p53基因蛋白定位及表达程度检测，并对比其差异，分析它们之间的关系。结果PCNA在ESH、EAH和EC3组病例中强阳性表达分别为16．7％、82．1％和96．2％，ESH与EAH、EC比较差异有统计学意义（P〈0．01），而EAH与EC比较差异无统计学意义（P〉0．05）。p16在ESH、EAH和EC3组病例中阳性表达分别为95．8％、46．4％和50．0％，ESH与EAH、Ec组比较差异有统计学意义（P〈0．05）；EAH与EC组比较差异无统计学意义（P〉0．05）。p53在ESH组无阳性表达病例，EAH组阳性率25％，EC组阳性率65．4％，3组病例之间比较差异均有统计学意义（P〈0．01）。结论PCNA、p53表达在子宫内膜增殖性病变、细胞恶性转化的进程中呈递增趋势，而p16趋于递减，提示细胞的过度增殖和增殖-凋亡相关基因的表达失衡在子宫内膜恶性转化过程中起重要作用。PCNA、p16和p53的异常表达可作为子宫内膜增生性疾病不同发展阶段的诊断及预测其生物学行为的参考指标。

Objective To investigate the expression of proliferation cell nuclear antigen （PCNA）, p16 gene and p53 gene in the endometrial simple hyperplasia（ESH） ,endometrial atypical hyperplasia （EAH） and endometrial carcinoma（EC）. Methods Determined the expression levels of PCNA ,p16 and p53 in the ESH, EAH and EC by using immunohistochemical technique, compared the differences and analyzed their relations. Results The strong positive rate of PCNA in the ESH,EAH and EC was 16. 7% ,82. 1% and 96. 2% respectively. The difference in PCNA positive rate between EAH, EC and ESH group had statistical significance （ P 〈 0. 01 ） ; Whereas there was no difference between EAH group and EC group （ P 〉 0. 05 ）. The positive rate of p16 protein was 95.8% ,46. 4% and 50. 0% in ESH,EAH and EC group respectively. The difference in p16 positive rate between EAH, EC and ESH group had statistical significance（ P 〈 0. 05 ） ;but there was no statistical difference between EAH and EC group（ P 〉0. 05）. There was no p53 positive case in ESH group,the positive rate of p53 in EAH and EC group was respectively 25% and 65.4%. There were statistical differences among the three groups （ P 〈 0. 01 ）. Conclusion The expressions of PCNA and p53 gradually increase in the progression of endometrial proliferation and neoplasia, but p16 decreases in this progression. It indicates that cell hyperproliferation and imbalance of proliferation- apoptosis gene expression play an important role in the progression of endometrial carcinogenesis. The abnormal expressions of PCNA ,p16 and p53 can be used as markers to diagnosis and forecast the different development of endometrial hyperplasia.