Liu Ming, Zhang Feng, Liu Shen, Zhao Wen, Zhu Jing, Zhang Xiaoli
Departments of Cardiothoracic Surgery.
Exp Ther Med. 2011 Sep;2(5):997-1001. doi: 10.3892/etm.2011.297. Epub 2011 Jun 27.
The objective of this study was to characterize the molecular events in the carcinogenesis of esophageal squamous cell carcinoma (ESCC) and to identify biomarkers for early detection of the disease. Matched precancerous and cancerous tissues resected from 34 esophageal cancer patients from Chongqing, southern China, were compared to evaluate the extent of loss of heterozygosity (LOH). Sixteen microsatellite markers on chromosome regions 3p, 4p, 5q, 8p, 9p, 9q, 11p, 13q and 17p were used for PCR-based LOH analysis. The overall frequency of LOH at the 16 microsatellite loci was significantly increased as the pathological status of the resection specimens changed from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and SCC (P<0.001). A total of 8 markers showed LOH in the LGD samples. In addition, heterozygosity was regained at 4 loci in the SCC samples of 4 patients, respectively, in comparison to the results for these loci in the HGD samples. The overall rate of LOH increased significantly with the deterioration of the lesions, indicating that tumorigenesis of the esophageal squamous epithelia is a progressive process involving accumulative changes in LOH. The 8 loci showing allelic loss in the LGD samples may be involved in the early-stage tumorigenesis of ESCC, and LOH analysis at these loci may help improve the early detection of this disease. Regain of heterozygosity found in certain patients suggests the possibility of genetic heterogeneity in the tumori-genesis of esophageal cancer.
本研究的目的是描述食管鳞状细胞癌（ESCC）致癌过程中的分子事件，并确定该疾病早期检测的生物标志物。对从中国南方重庆的34例食管癌患者切除的配对癌前组织和癌组织进行比较，以评估杂合性缺失（LOH）的程度。使用位于3p、4p、5q、8p、9p、9q、11p、13q和17p染色体区域的16个微卫星标记进行基于PCR的LOH分析。随着切除标本的病理状态从低级别发育异常（LGD）转变为高级别发育异常（HGD）和鳞状细胞癌（SCC），16个微卫星位点的总体LOH频率显著增加（P<0.001）。共有8个标记在LGD样本中显示出LOH。此外，与HGD样本中这些位点的结果相比，4例患者的SCC样本中分别有4个位点恢复了杂合性。LOH的总体发生率随着病变的恶化而显著增加，表明食管鳞状上皮的肿瘤发生是一个渐进过程，涉及LOH的累积变化。在LGD样本中显示等位基因缺失的8个位点可能参与了ESCC的早期肿瘤发生，对这些位点进行LOH分析可能有助于改善该疾病的早期检测。在某些患者中发现的杂合性恢复表明食管癌肿瘤发生中存在基因异质性的可能性。
