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目的 通过对食管黏膜高级别上皮内瘤变和鳞状细胞癌中的等位基因杂合子缺失(LOH)的检测,以期发现与食管鳞状细胞癌关系密切的抑癌基因。方法 应用显微切割,PCR扩增、凝胶电泳、放射自显影等技术,对照分析正常体细胞、食管鳞状上皮高级别上皮内瘤变和食管鳞状细胞癌组织中LOH的变化,并就各位点杂合子缺失率与患者的临床病理参数分别进行单因素分析。结果 高级别上皮内瘤变中7个位点的LOH依次为D13S802(40%)、D9S171(33%)、D13S267(320%)、D13S221(31%)、D9S942(30%)和D17S520(240%),而D17S1798在本组上皮高级别上皮内瘤变中未发现杂合子缺失。在食管鳞状细胞癌组织中,上述7个位点的LOH率依次为D13S267(71%),D13S802(58%),D17S520(55%)、D13S221(45%)、D9S942(43%)、D9S171(33%)和D17S1798(11%)。应用SPSS软件对7个微卫星序列的等位基因LOH率与患者的病理学分级、临床病理分期及是否有淋巴结转移进行单因素分析,差异均无显著性(P>0.05)。结论 (1)从正常黏膜到上皮内瘤变再到食管鳞癌的发生过程中,同时伴随基因异常的逐步积累。(2)13q12.12上的D13S802附近可能存在着主要与食管鳞状细胞癌早期发生有关的抑癌基因。(3)13q12.3上的D13S267附近、17p13.1上的D17S520和17p13.3上的D17S1798附近的基因可能与食管
Objective To detect alleles of heterozygosity (LOH) in esophageal mucosa with high-grade intraepithelial neoplasia and squamous cell carcinoma in order to find tumor suppressor genes closely related to esophageal squamous cell carcinoma. Methods The changes of LOH in normal somatic cells, high grade intraepithelial neoplasia of esophageal squamous cell carcinoma and esophageal squamous cell carcinoma were analyzed by microdissection, PCR amplification, gel electrophoresis and autoradiography. Unreduced heterozygosity at each locus and clinical pathological parameters of patients were univariate analysis. Results The LOH of 7 sites in high grade intraepithelial neoplasia were D13S802 (40%), D9S171 (33%), D13S267 (320%), D13S221 (31%), D9S942 (30%) and D17S520 (240% ), While D17S1798 in this group of epithelial high grade intraepithelial neoplasia found no loss of heterozygotes. In esophageal squamous cell carcinoma, the LOH rates of the above seven sites were D13S267 (71%), D13S802 (58%), D17S520 (55%), D13S221 (45%), D9S942 (43%), D9S171 (33%) and D17S1798 (11%). There was no significant difference (P> 0.05) between the LOH rates of 7 microsatellite loci and the pathological grade, clinical stage and lymph node metastasis of the 7 microsatellite loci by SPSS software. Conclusion (1) From normal mucosa to intraepithelial neoplasia to esophageal squamous cell carcinoma, accompanied by the gradual accumulation of genetic abnormalities. (2) Tumor suppressor genes that are mainly associated with the early occurrence of esophageal squamous cell carcinoma may exist near D13S802 on 13q12.12. (3) Genes near D13S267 on 13q12.3, D17S520 on 17p13.1, and D17S1798 on 17p13.3 may be associated with esophageal