Department of Histology, Medical University of Gdansk, Gdansk, Poland.
J Physiol Pharmacol. 2009 Oct;60 Suppl 4:63-70.
FHIT gene, mapped at FRA3B site, encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism. Decreased FHIT gene expression was previously observed in various types of human cancer, however, quantification of FHIT mRNA was seldom performed.
To investigate loss of heterozygosity (LOH) at FRA3B, expression of FHIT gene at the mRNA and protein levels in sporadic colorectal carcinoma (CRC) and benign colon adenoma.
FHIT mRNA was quantified by the validated realtime PCR (QPCR) in tumor samples of 84 CRC patients and mucosal biopsies of 15 adenomas, in comparison to 37 control patients, whereas subgroup of 57 CRC, 10 adenoma and 10 control cases were selected for immunohistochemical (IHC) detection of the native FHIT protein and LOH determination at FRA3B.
Higher level of FHIT mRNA was found in 86% of CRC (P<0.001) and 60% of adenomas (P=0.016). IHC showed comparable results to QPCR (P=0.003), revealing the strongest presence of FHIT protein in Dukes' C/D stages (P<0.001) and N1/N2 lymph nodes metastasis in CRC (P=0.04). FHIT gene expression and Dukes' and G staging were positively correlated in CRC as analyzed by QPCR and IHC. Deletion analysis of the fragile FRA3B site revealed the highest LOH frequency at D3S1234 in 32.5% of CRC informative cases, however, LOH did not correspond to QPCR, IHC or clinical-pathological variables.
Our data suggest that reduction or absence of the FHIT gene expression is not a prerequisite for colorectal cancer development and progression.
脆性组氨酸三联体（FHIT）基因位于 FRA3B 位点，编码人类二腺苷三磷酸水解酶，参与细胞周期和核苷酸代谢的调节。先前在各种类型的人类癌症中观察到 FHIT 基因表达降低，但 FHIT mRNA 的定量很少进行。
研究散发性结直肠癌（CRC）和良性结肠腺瘤中 FRA3B 的杂合性丢失（LOH）、FHIT 基因在 mRNA 和蛋白水平上的表达。
在 84 例 CRC 患者的肿瘤样本和 15 例腺瘤的黏膜活检中，通过验证的实时 PCR（QPCR）定量 FHIT mRNA，与 37 例对照患者进行比较，选择 57 例 CRC、10 例腺瘤和 10 例对照病例进行免疫组化（IHC）检测天然 FHIT 蛋白和 FRA3B 处 LOH 的确定。
CRC（P<0.001）和腺瘤（P=0.016）中 FHIT mRNA 水平较高的分别为 86%和 60%。IHC 与 QPCR 结果相当（P=0.003），显示 FHIT 蛋白在 Dukes' C/D 期（P<0.001）和 CRC 中 N1/N2 淋巴结转移（P=0.04）最强。通过 QPCR 和 IHC 分析，CRC 中 FHIT 基因表达与 Dukes 分期和 G 分期呈正相关。脆弱的 FRA3B 位点的缺失分析显示，32.5%的 CRC 信息病例中在 D3S1234 处出现最高的 LOH 频率，但 LOH 与 QPCR、IHC 或临床病理变量不对应。
我们的数据表明，FHIT 基因表达的减少或缺失不是结直肠癌发生和发展的必要条件。
