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

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...

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Main Authors: Mohammad Mahdi Forghanifard, Elham Emami Vahid, Ezzat Dadkhah, Mehran Gholamin, Samaneh Broumand Noghabi, Martha Ghahraman, Mehdi Farzadnia, Mohammad Reza Abbaszadegan
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2016-07-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:http://ijbms.mums.ac.ir/article_7356_09e6f16f2c5afde2adc9d97dfc5c4f02.pdf
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author Mohammad Mahdi Forghanifard
Elham Emami Vahid
Ezzat Dadkhah
Mehran Gholamin
Samaneh Broumand Noghabi
Martha Ghahraman
Mehdi Farzadnia
Mohammad Reza Abbaszadegan
author_facet Mohammad Mahdi Forghanifard
Elham Emami Vahid
Ezzat Dadkhah
Mehran Gholamin
Samaneh Broumand Noghabi
Martha Ghahraman
Mehdi Farzadnia
Mohammad Reza Abbaszadegan
author_sort Mohammad Mahdi Forghanifard
collection DOAJ
description 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 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. Results: 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). 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.
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spelling doaj.art-eda3b1d4122b4708978f01fc0646d8282022-12-21T21:21:33ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742016-07-011977267337356Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patientsMohammad Mahdi Forghanifard0Elham Emami Vahid1Ezzat Dadkhah2Mehran Gholamin3Samaneh Broumand Noghabi4Martha Ghahraman5Mehdi Farzadnia6Mohammad Reza Abbaszadegan7Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, IranDivision of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, IranSchool of Systems Biology, George Mason University, Manassas, Virginia, U.S.ADivision of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of hematopathology, Central Laboratory, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDivision of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, IranCancer Molecular Pathology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDivision of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran|Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranObjective(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 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. Results: 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). 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.http://ijbms.mums.ac.ir/article_7356_09e6f16f2c5afde2adc9d97dfc5c4f02.pdfEsophageal squamous cell -carcinomaLoss of heterozygosityMicrosatellite instability
spellingShingle Mohammad Mahdi Forghanifard
Elham Emami Vahid
Ezzat Dadkhah
Mehran Gholamin
Samaneh Broumand Noghabi
Martha Ghahraman
Mehdi Farzadnia
Mohammad Reza Abbaszadegan
Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
Iranian Journal of Basic Medical Sciences
Esophageal squamous cell -carcinoma
Loss of heterozygosity
Microsatellite instability
title Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
title_full Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
title_fullStr Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
title_full_unstemmed Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
title_short Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
title_sort loss of heterozygosity and microsatellite instability as predictive markers among iranian esophageal cancer patients
topic Esophageal squamous cell -carcinoma
Loss of heterozygosity
Microsatellite instability
url http://ijbms.mums.ac.ir/article_7356_09e6f16f2c5afde2adc9d97dfc5c4f02.pdf
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