喉鳞癌组织中脆性组氨酸三联体基因编码外显子纯合性缺失检测

Homozygous deletion of coding exons of FHIT gene in laryngeal squamous cell carcinoma tissue

目的:探讨喉鳞癌(LSCC)组织中脆性组氨酸三联体(FHIT)基因编码外显子纯合性缺失及其临床意义。方法:分别采用外显子特异PCR技术及免疫组化SP法检测41例LSCC(肿瘤发生部位位于声门上15例,声门24例,声门下2例;TNM分期Ⅰ期10例,Ⅱ期13例,Ⅲ期15例,Ⅳ期3例;病理分级:高分化15例,中分化18例,低分化8例;淋巴结转移阳性15例,阴性26例)及其相对应的喉正常黏膜组织中FHIT基因全部编码外显子E5～E9纯合性缺失及增殖细胞核抗原(PCNA)表达,并分析其与临床病理特征及PCNA的关系。结果:41例喉正常黏膜组织中,E5～E9无1例发生纯合性缺失。LSCC组织中,E5～E9纯合性缺失率分别为26.8%(11/41)、14.6%(6/41)、9.8%(4/41)、29.3%(12/41)和7.3%(3/41)。FHIT基因编码外显子总纯合性缺失率为41.5%(17/41),且与患者TNM分期、淋巴结转移及复发有关(P<0.05)。FHIT基因编码外显子纯合性缺失与PCNA标记指数有明显的负相关关系(P<0.05)。结论:LSCC组织中FHIT基因编码外显子纯合性缺失可能为其基因失活的重要机制之一,可作为检测LSCC生物学行为的重要标志。

Aim ： To investigate the frequencies of homozygous deletion of entire coding exons of fragile histidine triad （FHIT） gene in laryngeal squamous cell carcinoma （LSCC） tissue and its clinical significance. Methods： Exon-specific PCR amplification technique and SP immunohistochemical technique were used to detect homozygous deletion of entire coding exons of FHIT and expression of PCNA in 41 cases of LSCC and its normal laryngeal tissue. Results： No homozygous deletion of exon of FHIT was found in 41 cases of normal tissue. The rate of homozygous deletion of Exon5 - Exon9 was 26.8%（11/41）, 14.6%（6/41）, 9.8%（4/41）, 29.3%（12/41）and7.3%（3/41）, respectively. The overallhomozygous deletion rate of coding exons of FHIT gene was 41.5% （ 17/41 ） and it was related to the tumor TNM stage, lymph node metastasis and tumor relapse （P 〈 0.05）. In LSCC, the negative correlation was found between homozygous deletion of entire coding exons of FHIT and expression of PCNA （ P 〈 0.05 ）. Conclusion ： In LSCC, the homozygous deletion of coding exons is one of important inactive mechanisms of FHIT gene, which might be useful for evaluating the biological behavior of LSCC.