Forghanifard Mohammad Mahdi, Vahid Elham Emami, Dadkhah Ezzat, Gholamin Mehran, Noghabi Samaneh Broumand, Ghahraman Martha, Farzadnia Mehdi, Abbaszadegan Mohammad Reza
Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2016 Jul;19(7):726-33.
Variation in microsatellite sequences that are dispersed in the genome has been linked to a deficiency in cellular mismatch repair system and defects in several genes of this system are involved in carcinogenesis. Our aim in this study was to illustrate microsatellite DNA alteration in esophageal cancer.
DNA was extracted from formalin fixed paraffin embedded (FFPE) tissues from surgical and matched margin-normal samples. Microsatellite instability (MSI) and loss of heterozygosity (LOH) were studied in 50 cases of esophageal squamous cell carcinoma (ESCC) by amplifying six microsatellite markers: D13S260 (13q12.3), D13S267 (13q12.3), D9S171 (9p21), D2S123 (2p), D5S2501 (5q21) and TP53 (17p13.1) analyzed on 6% denaturing polyacrylamide gel electrophoresis.
Statistical analysis indicated a near significant reverse correlation between grade and LOH (P= 0.068, correlation coefficient= -0.272). Specifically, increased LOH in tumor DNA has a significant correlation with increased differentiation from poorly differentiated to well differentiated tumors (P= 0.002 and P= 0.016 respectively). In addition, higher number of chromosomal loci with LOH showed a reverse correlation with lymph node metastasis (P= 0.026, correlation coefficient= -0.485). Furthermore, there was a positive correlation between addiction and MSI (P= 0.026, correlation coefficient= 0.465).
Microsatellite DNA alterations may be a prognostic tool for detection and the evolution of prognosis in patients with SCC of esophagus. It can be concluded that regional lymph node metastasis would be less likely with increased heterozygote loci and addiction with any of opium, cigarette, water pipe or alcohol can be a susceptibility factor(s) for MSI.
分散于基因组中的微卫星序列变异与细胞错配修复系统缺陷有关，该系统中多个基因的缺陷参与致癌过程。本研究的目的是阐明食管癌中微卫星DNA的改变。
从手术切除的福尔马林固定石蜡包埋（FFPE）组织及其配对的切缘正常样本中提取DNA。通过扩增六个微卫星标记：D13S260（13q12.3）、D13S267（13q12.3）、D9S171（9p21）、D2S123（2p）、D5S2501（5q21）和TP53（17p13.1），对50例食管鳞状细胞癌（ESCC）进行微卫星不稳定性（MSI）和杂合性缺失（LOH）研究，并在6%变性聚丙烯酰胺凝胶电泳上进行分析。
统计分析表明，分级与LOH之间存在近乎显著的负相关（P = 0.068，相关系数 = -0.272）。具体而言，肿瘤DNA中LOH增加与肿瘤从低分化到高分化的分化程度增加显著相关（分别为P = 0.002和P = 0.016）。此外，具有LOH的染色体位点数量增加与淋巴结转移呈负相关（P = 0.026，相关系数 = -0.485）。此外，成瘾与MSI之间存在正相关（P = 0.026，相关系数 = 0.465）。
微卫星DNA改变可能是食管鳞状细胞癌患者预后检测和预后演变的一种工具。可以得出结论，杂合子位点增加时区域淋巴结转移的可能性较小，并且吸食鸦片、香烟、水烟或饮酒中的任何一种成瘾都可能是MSI的一个易感因素。
