定性及定量分析脆性组氨酸三联体基因蛋白表达在食管癌变过程中的临床意义

Clinical value in quantitative and qualitative detection of Fhit protein in esophageal carcinomatous change

目的定性和定量分析脆性组氨酸三联体基因蛋白(Fhit蛋白)在食管癌及癌前病变(不典型增生)组织中的表达,探讨Fhit蛋白与食管癌发生发展的关系。方法收集色素内镜初筛并经组织病理学证实标本94例,应用免疫组化及流式细胞术(FCM),定性及定量检测Fhit蛋白在食管癌变过程中的表达情况。结果①从食管鳞状上皮→不典型增生(癌前病变)→原位癌→浸润癌,随着食管病变的加重,定性及定量检测Fhit蛋白表达均呈逐渐降低趋势;②免疫组化结果显示:正常组、不典型增生Ⅰ级组、不典型增生Ⅱ级组、不典型增生Ⅲ级组、原位癌组、浸润癌组中Fhit蛋白表达分别为82.35%、75.00%、43.75%、35.29%、30.00%、33.33%;正常组与食管不典型增生Ⅰ级组Fhit蛋白表达差异无统计学意义(P>0.05),与其余各组相比差异有统计学意义(P<0.05);浸润癌组与正常组、不典型增生Ⅰ级组差异均有统计学意义(P<0.05),浸润癌组与不典型增生Ⅱ级、Ⅲ级组、原位癌组差异无统计学意义(P>0.05);③FCM结果显示:不典型增生Ⅰ级、Ⅱ级组间Fhit蛋白表达量差异有统计学意义(P<0.001),不典型增生Ⅱ级、Ⅲ级组间差异有统计学意义(P<0.05),不典型增生Ⅱ级与正常组间差异有统计学意义(P<0.001),不典型增生Ⅲ级与食管癌组间差异无统计学意义(P>0.05)。结论Fhit蛋白表达缺失是食管癌变过程的早期事件,随病理组织学分级的增高Fhit蛋白表达阳性率逐渐降低,其蛋白表达的缺失在食管癌发生、发展过程中可能起着重要作用。

Objective To investigate the change of Fhit protein expression in esophageal carcinoma and precancerous lesions（atypical hyperplasia tissues）,and to explore the relationship between Fhit protein and esophageal carcinoma. Methods On the basis of mucosal iodine staining and histological diagnosis,expression of Fhit protein in specimens from 94 cases were measured qualitatively by immunohistochemical method and quantitatively by flow cytometry analysis method. Results ①With the increase of histopathologic grade,the expression Fhit protein reduced gradually. ②The result of immunohistochemical method showed there was no remarkable correlation between normal group and atypical hyperplasia I group（ P 〉 0.05）. Fhit protein expressions in normal group and other groups were respectively with significant statistical differences （ P 〈0.05）. There was no remarkable correlation between atypical hyperplasia Ⅱ , Ⅲ group, carcinoma in situ group and squamous cell carcinoma（ P 〉0.05）. Fhit protein expression in squamous cell carcinoma and normal group, atypical hyperplasia I group were respectively with significant statistical differences（ P 〈0. 05）. ③The result of flow cytometry analysis showed Fhit protein expressions in atypical hyperplasia I and atypical hyperplasia Ⅱ were respectively with significant statistical differences（ P 〈0. 001）. The expression in atypical hyperplasia Ⅱ and atypical hyperplasia Ⅲ were respectively with significant statistical differences （ P 〈0.05）. The expressions in atypical hyperplasiaⅡand normal group were respectively with significant statistical differences （P 0.001）. There was no remarkable correlation between atypical hyperplasia Ⅲ group and squarnous cell carcinoma（ P 〉0.05）. Conclusion With the increase of histopathologic grade,the expression of Fhit protein reduced gradually. The negative expression of Fhit protein takes place early and possibly plays an important role in occurrence of esophageal cancer.