17号染色体微卫星不稳定性和杂合性丢失与非小细胞肺癌的关系

目的　明确１７ 号染色体微卫星不稳定性（ＭＩ） 和杂合性丢失（ＬＯＨ） 与非小细胞肺癌（ＮＳＣＬＣ） 的关系。方法　对３５ 例ＮＳＣＬＣ肿瘤切除组织和肿瘤旁正常组织，采用聚合酶链反应微卫星长度多态性分析方法检测了１７ 号染色体上４ 个微卫星位点ＴＰ５３（１７ｐ１３－１）、ＴＨＲＡ１（１７ｑ１１－２１２）、Ｄ１７Ｓ５７９（１７ｑ１２２１）、Ｄ１７Ｓ８５５（１７ｑ２１） 的ＭＩ和ＬＯＨ。结果　３５ 例ＮＳＣＬＣ中，１７ 号染色体ＭＩ和（或）ＬＯＨ的发生率为６３％ （２４／３５），其中ＭＩ为４０％ （１４／３５） ，ＬＯＨ 为３１％ （１１／３５）。同时表现有ＭＩ和ＬＯＨ 为９％ （３／３５） 。早期ＮＳＣＬＣ（ Ⅰ期和Ⅱ期） １７ 号染色体ＭＩ和（ 或）ＬＯＨ 发生率为７９％ （１５／１９），明显大于晚期（ Ⅲ期）ＮＳＣＬＣ（４４％ ，７／１６，Ｐ＜０－０５） 。无纵隔淋巴结转移的ＮＳＣＬＣ的ＭＩ和（ 或）ＬＯＨ 发生率（８７％ ） 亦明显大于已有纵隔淋巴结转移者（４８％ ），Ｐ＜ ０－０５。ＭＩ和（ 或）ＬＯＨ 在不同肿瘤组织类型以及不同组织细胞分化程度之间差异无显著性，Ｐ＞０．０５。结论　１７ 号染色体ＭＩ和ＬＯＨ 在ＮＳＣＬＣ的发生中可

Studies of microsatellite instability and loss of heterozygosity at chromosome 17 in non small cell lung carcinoma

OBJECTIVE: To identify the presence of microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung carcinoma (NSCLC). METHODS: Four microsatellite markers TP53(17p13.1), THRA1 (17q11.2-12), D17S579(17q12-21) and D17S855(17q21) were used to examine 35 cases of NSCLC tumor-normal paired tissues for MI and LOH at chromosome 17 using PCR based analysis. RESULTS: 22 of 35 tumors(63%) displayed MI or LOH. 14 tumors(40%) exhibited MI, 11 tumors(31%) exhibited LOH, while 3 tumors (9%) exhibited MI and LOH concurrently. The frequency of MI or LOH was obviously higher in the early-stage(stages I and II, 79%) than in the advanced-stage (stage III, 44%), P < 0.05. However, the frequency of MI or LOH had no significant difference between high-grade differentiated NSCLC tumors and low-grade ones, P > 0.05. No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC, P > 0.05. CONCLUSIONS: The results suggest that MI and LOH at chromosome 17 may play a significant role in the development of NSCLC. The high frequency of MI or LOH in the early-stage tumors indicates that these genetic alterations could occur early during NSCLC development.