结直肠癌脆性组氨酸三联体蛋白表达丢失研究

目的 探讨结直肠癌中脆性组氨酸三联体（FHIT）基因蛋白表达状况及其与临床病理指标的可能关系。方法 采用兔抗人FHIT蛋白抗体和枸橼酸－微波－SP免疫组织化学方法检测60例甲醛固定、石蜡包埋的结直肠癌蜡块标本中FHIT表达状况并分析其与组织学分级、Dukes分期以及5年生存率的关系。结果 癌组织FHIT表达强度较正常黏膜高者为21例（35．0％）,较正常黏膜低者为33例（55．0％）,与正常黏膜基本相等者为6例（10．0％）。FHIT蛋白低表达癌在癌组织学分级中的分布为I级癌7／16,Ⅱ级癌14／30,Ⅲ级癌12／14,各级癌组间比较,差异有显著性（P＜0．05）。FHIT蛋白低表达癌在Dukes分期中的分布为A组癌5／11,B期癌12／28,C期癌16／21,已伴淋巴结转移组的C期癌与未转移组的A、B期癌比较,差异有显著性（P＜0．05）。39例获访病例中,FHIT蛋白低表达癌在5年随访病例组中的分布为5年生存组为13／25,5年死亡组为12／14,组间比较差异有显著性（P＜0．05）。结论 结直肠癌FHIT表达状况可能与组织学分级、Dukes分期以及5年生存率相关,提示FHIT表达降低可能对结直肠癌的演化和进展具有一定重要作用,并可能成为一个新的预后指标。

Loss of fragile histidine triad expression in colorectal carcinoma

OBJECTIVE: To investigate the expression of fragile histidine triad (FHIT) gene protein, FHIT and the possible relationship between FHIT expression and clinicopathological indices in colorectal carcinoma. METHODS: Detecting FHIT protein expression in 60 cases of formalin-fixed, paraffin-embedded colorectal carcinoma by citrate-microwave-SP immunohistochemical method, and analyzing its relationship to histological grade, Dukes' stage and 5-year survival rate. RESULTS: 55% of the carcinomas showed a marked loss or absence of FHIT expression compared with their matched normal mucosa. Carcinomas with reduced expression of FHIT correlated with their histological grade, Dukes' stage (P < 0.05) and 5-year survival rate. The distribution of decreased expression of FHIT was 7/16 in grade I carcinoma, 14/30 in grade II, 12/14 in grade III, respectively. The correlation between decreased expression of FHIT and Dukes' staging was 5/11 in stage A, 12/28 in stage B, and 16/21 in stage C. The difference between stage A, B with no lymph nodes metastases and the stage C with lymph nodes metastases was of significance (P < 0.05). The follow-up data of 39 cases showed that in the 5-year survival group, 13/25 were of the low FHIT expression carcinomas, while in 5-year deceased group 12/14 were of the low FHIT expression carcinomas (P < 0.05). CONCLUSIONS: The reduced expression of FHIT may be associated with decreasing differentiation, metastasis and 5-year survival rate in colorectal carcinoma. It is suggested that decreased FHIT expression plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in colorectal carcinoma.