子宫颈癌FHIT基因表达与杂合性丢失

Abnormal expression and loss of heterozygosity of the FHIT gene in cervical carcinomas

目的 探讨抑癌基因FHIT基因在子宫颈癌发生中的作用及其失活的可能机制。方法 选取FHIT基因内 2个微卫星位点D3S130 0和D3S12 34,对 5 6例经显微切割分离肿瘤组织的原发性子宫颈癌进行杂合性丢失 (LOH)分析 ,同时采用免疫组化方法 (S P法 )检测FHIT的表达情况。结果 D3S130 0和D3S12 34的LOH发生率分别为 36 2 % (17/ 4 7)、32 7% (16 /4 9) ,5 2 % (2 9/ 5 6 )的子宫颈癌组织至少在一个位点存在LOH。 5 7 1%的子宫颈癌FHIT表达减弱或缺失 ,其中 71 9%存在FHIT基因LOH ,FHIT低表达与FHIT基因LOH之间有相关性 (P <0 0 1)。子宫颈鳞癌组织的LOH发生率及FHIT低表达率均高于腺癌 (6 4 3%vs 14 3% ,6 9 0 %vs 2 1 4 % ,P <0 0 5 )。子宫颈鳞癌LOH发生率及FHIT低表达与组织学分级、FI GO分期均不相关 (P >0 0 5 )。结论 FHIT基因可能在子宫颈鳞癌发生中起重要作用 。

Purpose To investigate the possible role of tumor suppressor gene, fragile histidine triad (FHIT) gene in cervical carcinogenesis and the mechanisms for inactivation of this gene. Methods Forty six microdissected archival tissues of primary cervical carcinoma were evaluated for loss of heterozygosity (LOH) at two microsatellite loci within the FHIT gene. In addition, FHIT protein was examined by immunohistochemical staining. Results LOH was detected in 36 2% and 32 7% of informative cases at D3S1300 and D3S1234, respectively. Fifty two percent of the cases were found deleted at least at one locus. Thirty two out of 56 cervical carcinomas (57 1%) displayed reduced or absent FHIT expression, 71 9% of which had FHIT gene LOH. A statistically significant relationship was found between FHIT gene LOH and abnormal FHIT expression ( P <0 01). It showed that significantly higher frequency of both FHIT gene LOH and FHIT abnormal expression in squamous carcinomas than in adenocarcinomas(64 3% vs 14 3%,69 0% vs 21 4%, P <0 05). No apparent correlation was observed between FHIT LOH and histological grades, and FIGO stage ( P >0 05). Conclusions FHIT gene may play an important role in carcinogenesis of squamous cell cervical carcinoma. Loss of heterozygosity may be an important mechanism for inactivation of FHIT gene.