胃癌Fhit蛋白表达缺失的临床病理意义

Loss of fragile histidine triad protein expression and its clinicopathological significance in gastric cancer

目的:探讨76例胃癌Fhit蛋白表达与临床病理的关系. 方法:采用免疫组化方法,检测76例胃癌、58例紧邻癌旁的异常增生和10例正常胃黏膜的Fhit表达并分析其与组织学分级、临床分期以及预后的关系. 结果:癌组织Fhit表达缺失为48/76例(63.2%),紧邻癌旁的异常增生黏膜缺失为36/58例(62.1%),而正常胃黏膜为0/10,相差有非常显著性(P=0.000)Fhit蛋白缺失癌在癌组织学分级中的分布为Ⅰ-Ⅱ级癌35.7%(10/28),Ⅲ级癌79.2%(38/48),相差有非常显著性(P=0.000).Fhit蛋白缺失癌在临床分期中的分布为Ⅰ-Ⅱ期癌为43.8%(14/32), Ⅲ-Ⅳ期癌77.3%(34/44),相差有非常显著性(P=0.004).Fhit 蛋白缺失癌在转移状况组的分布为转移癌74.1%(40/54), 未转移癌为36.4%(8/22),相差有非常显著性(P=0.003). 随访资料显示Fhit蛋白缺失癌的中位生存时间为33 mo,而Fhit蛋白表达癌者为71 mo,相差有非常显著性(Log rank=20.78:P=0.000). 结论:Fhit蛋白为一种重要的抑癌蛋白,其表达缺失状况可能与胃癌的发生、侵犯、转移以及患者的预后相关.

AIM: To investigate the expression of fragile histidine triad protein, Fhit and the possible relationship between its expression and clinicopathological indices in gastric carcinoma. METHODS: Fhit protein expression was detected in 76 cases of gastric carcinoma, 58 dysplasia and 10 normal mucosae by immunohistochemical method to analyse its relationship to histological grade, clinical stage, metastatic status and prognosis. RESULTS: The loss of Fhit protein expression was detected in 48/76 (63.2%) cases of cancer tissue, 36/58 (62.1%) cases of adjacent dysplastic tissue and 0/10 cases of normal gastric mucosa. There was a significant difference in the expression of Fhit protein between cancer or adjacent dysplastic tissue and normal gastric mucosa (P =0.000). It was also showed that loss of Fhit protein expression was found first in 35.7% (10/28) of grade MI, and in 79.2% (38/48) of grade Ⅲ (P= 0.000); second in 43.8% (14/32) of stage MI, whereas in 77.3% (34/44) of stage Ⅲ-Ⅳ (P= 0.004); and last in 36.4% (8/22) of tumors without metastasis but in 74.1% (40/54) of those with metastasis (P = 0.003). The significant difference in the loss of expression of Fhit was found between cancers on different histological grade, clinical stage and metastatic status, respectively. Follow-up data showed that there was a significant difference in median survival time between carcinomas with loss of Fhit (33 months) and those without (71 months) (Log rank = 20.78; P= 0.000). CONCLUSION: Fhit protein is an important tumor suppressor protein. Loss of Fhit protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis in gastric carcinoma.