Fhit蛋白和PCNA在子宫内膜癌中的表达及意义

目的探讨正常子宫内膜、子宫内膜非典型增生和子宫内膜腺癌组织中脆性组氨酸三联体(Fhit)蛋白和增殖细胞核抗原(PCNA)的表达及与临床、病理的关系。方法应用免疫组织化学SP法检测正常子宫内膜、子宫内膜非典型增生和子宫内膜腺癌组织中Fhit蛋白和PCNA的表达。结果正常子宫内膜中Fhit蛋白和PCNA的阳性表达率或高增殖率分别为100%和10%;非典型增生内膜中Fhit蛋白和PCNA的阳性表达率或高增殖率分别为66.7%和11.1%;子宫内膜癌组织中Fhit蛋白和PCNA表达阳性率或高增殖率均为54.4%。Fhit蛋白与肿瘤组织的手术-病理分期、分化程度相关。PCNA在子宫内膜癌中表达与肿瘤组织的分化程度相关。Fhit蛋白表达阳性子宫内膜腺癌中PCNA高增殖率为36.7%,Fhit蛋白表达阴性子宫内膜腺癌中PCNA高增殖率为79.9%,二者呈负相关。结论①Fhit蛋白和PCNA异常表达与子宫内膜癌的发生、发展密切相关,二者可能在子宫内膜由良性到恶性的转变过程中,以及恶性肿瘤进展中起了重要作用。②Fhit蛋白的表达和PCNA的表达呈负相关,提示较高的增殖能力,可能与Fhit蛋白缺失有关,后者通过直接或间接的作用增强癌细胞的增殖活性。③Fhit蛋白可能作为肿瘤生物学行为的标志,成为子宫内膜癌治疗的新靶向。

The expression and significana of fragile histidine triad protein and proliferating cell nuclear antigen in endometrial carcinoma

Objective To define the expression of Fhit protein and PCNA in normal endometrium,endometrial carcinoma and atypical hyperplasia of endometrium and the association with the clinic and pathology. Methods The expression of Fhit protein and PCNA was detected by immunohistochemistry in histologically normal endometrium for 20 cases, endometrial adenocarcinoma for 57 cases, and atypical hyperplasia of endometrium for 9 cases. Results The positive expression of Fhit protein was observed in all normal endometrium cases (100%), and the rate of higher proliferation was 10%,the positive expression rate of Fhit protein was the same as the rate of higher proliferation in carcinoma cases, they were all 54.4%. In atypical hyperplasia of endometrium, the positive expression rate of Fhit protein and the higher proliferation rate were 66.7% and 11.1% respectively. There was a higher Fhit expression rate of normal tissue than those endometrial adenocarcinomas, on the contrary to the rate of higher proliferation of PCNA. The proportion of positive Fhit protein in those carcinomas at stage Ⅰ～Ⅱ 63.4% and in those at stages Ⅲ～Ⅳ 31.3%. The positive expression rate of Fhit protein of G1 G2 G3 was 75%, 50%,and 33% respectively. Loss of Fhit expression was associated with high malignant potential, including advanced surgical stage and high histological grade. The higher proliferation rate of PCNA of G1 G2 G3 was 30%,59% and 80%,respectively. Abnormal PCNA expression was associated with high histological grade. The higher proliferation rate of these cases with positive expression of Fhit was 36.7%, while it was 79.9% of these with negative Fhit expression. Conclusion The abnormal expression of Fhit protein and PCNA were important genetic events associated with the genesis and development of endometrial carcinoma. Loss of Fhit expression was associated with high malignant potential, including advanced surgical stage and high histological grade. Abnormal PCNA expression was associated with high histological grade. ②Our observations suggested that Fhit could interact with PCNA, abnormal expression of PCNA may be result from the absent or reductive expression of Fhit protein.3 Fhit protein may be a new target for the treatment of endometrial carcinoma.