Wu Qinghua, Shi Huirong, Suo Zhenhe, Nesland Jahn M
Department of Obstetrics and Gynecology, the First Affiliated Hospital, Zhengzhou University, Henan, China.
Ultrastruct Pathol. 2003 Nov-Dec;27(6):417-22. doi: 10.1080/01913120390250329.
Aberrant transcription of the FHIT gene has been observed in many solid tumors, suggesting that 5'-CpG island methylation of the FHIT gene is involved in tumor development. The authors investigated the status of the 5'-CpG island methylation of the FHIT gene and protein expression in a series of 40 cervical carcinomas and 10 normal cervical epithelial samples, and correlated the data with clinicopathological findings. Methylation-specific PCR was applied to detect the incidence of the 5'-CpG island methylation, and immunohistochemistry was used for FHIT protein staining. 5'-CpG island methylation of the FHIT gene was detected in 40% (16/40) of the cervical cancer samples and in none of normal cervical epithelial specimens. Furthermore, the 5'-CpG island methylation was positively associated with clinical stage (p=.002). All the normal cervical epithelial samples (10/10) and 90% (36/40) of the cervical carcinomas were positive when the unmethylated primer pair was applied. Of the 16 cervical carcinomas with 5'-CpG island methylation of the FHIT gene by PCR, 15 showed reduced FHIT protein expression. This study suggests that 5'-CpG island methylation plays an important role in inactivation of the FHIT gene in cervical cancer.
在许多实体瘤中均观察到FHIT基因的异常转录，这表明FHIT基因的5'-CpG岛甲基化与肿瘤发展有关。作者研究了40例宫颈癌和10例正常宫颈上皮样本中FHIT基因的5'-CpG岛甲基化状态及蛋白表达情况，并将这些数据与临床病理结果相关联。采用甲基化特异性PCR检测5'-CpG岛甲基化的发生率，免疫组化用于FHIT蛋白染色。在40%（16/40）的宫颈癌样本中检测到FHIT基因的5'-CpG岛甲基化，而在正常宫颈上皮标本中均未检测到。此外，5'-CpG岛甲基化与临床分期呈正相关（p = 0.002）。当使用未甲基化引物对时，所有正常宫颈上皮样本（10/10）和90%（36/40）的宫颈癌样本均呈阳性。在通过PCR检测到FHIT基因5'-CpG岛甲基化的16例宫颈癌中，15例显示FHIT蛋白表达降低。本研究表明，5'-CpG岛甲基化在宫颈癌FHIT基因失活中起重要作用。
