Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients

  • سال انتشار: 1395
  • محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 19، شماره: 7
  • کد COI اختصاصی: JR_IJBMS-19-7_005
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 304
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نویسندگان

Mohammad Mahdi Forghanifard

Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

Elham Emami Vahid

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Ezzat Dadkhah

School of Systems Biology, George Mason University, Manassas, Virginia, U.S.A

Mehran Gholamin

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Samaneh Broumand Noghabi

Department of hematopathology, Central Laboratory, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Martha Ghahraman

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Mehdi Farzadnia

Cancer Molecular Pathology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Mohammad Reza Abbaszadegan

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

چکیده

Objective(s): 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. Materials and Methods: 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 ۵۰ cases of esophageal squamous cell carcinoma (ESCC) by amplifying six microsatellite markers: D۱۳S۲۶۰ (۱۳q۱۲.۳), D۱۳S۲۶۷ (۱۳q۱۲.۳), D۹S۱۷۱ (۹p۲۱), D۲S۱۲۳ (۲p), D۵S۲۵۰۱ (۵q۲۱) and TP۵۳ (۱۷p۱۳.۱) analyzed on ۶% denaturing polyacrylamide gel electrophoresis. Results: Statistical analysis indicated a near significant reverse correlation between grade and LOH (P= ۰.۰۶۸, correlation coefficient= -۰.۲۷۲). Specifically, increased LOH in tumor DNA has a significant correlation with increased differentiation from poorly differentiated to well differentiated tumors (P= ۰.۰۰۲ and P= ۰.۰۱۶ respectively). In addition, higher number of chromosomal loci with LOH showed a reverse correlation with lymph node metastasis (P= ۰.۰۲۶, correlation coefficient= -۰.۴۸۵). Furthermore, there was a positive correlation between addiction and MSI (P= ۰.۰۲۶, correlation coefficient= ۰.۴۶۵). Conclusion: 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.

کلیدواژه ها

Esophageal squamous cell -carcinoma, Loss of heterozygosity, Microsatellite instability

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