Mide Kanseri ve Komşu Non-Tümoral Epitelde Epstein Barr Virüsü Pozitifliğinin Sıklığı

Yıl 2026, Cilt: 16 Sayı: 1 , 167 - 174 , 15.03.2026

Abdulkadir Yasir Bahar , Seda Keskin Gökmen , Emine Kılınç , Selin Fitnet Görücü , Özge Duymaz Gümüştaş , Rabia Hurşitoğlu

https://doi.org/10.16919/bozoktip.1727058

https://izlik.org/JA34PC35YU

Öz

Amaç
Epstein-Barr virüsüyle ilişkili mide kanseri, Kanser Genom Atlası Programı tarafından tanımlanan dört moleküler alt tipten biridir. Epstein-Barr virüsüyle ilişkili mide kanseri insidansı etnik ve coğrafi farklılıklar gösterir. Bu çalışmanın amacı mide kanseri dokularında ve bitişik tümör dışı epitelde EBV sıklığını araştırmaktır.
Gereç ve Yöntemler
EBV pozitifliği, Ocak 2008 ile Ağustos 2023 arasında merkezimizde mide karsinomu tanısı konulan ve gastrektomi geçiren 101 hastanın tümör dokularında kromojenik EBER-ISH ile değerlendirildi. Mide kanserinde EBV insidansı, sağ kalım ve klinikopatolojik prognostik faktörler arasındaki bağlantı istatistiksel olarak değerlendirildi.
Sonuçlar
EBV, 101 vakanın 6'sında (%5,9) tümör dokusunda pozitifti. Ek olarak, 10 vakada (%9,9) tümöre bitişik intestinal metaplazi alanlarında ve 13 vakada (%12,9) tümöre bitişik normal gastrik mukozada pozitif boyanma tespit edildi. EBV ile ilişkili gastrik kanserli 6 vakanın hepsi erkekti, 4'ü diffüz histolojik tipteydi ve 3'ü histolojik derece 3'tü, 4'ünde lenf nodu metastazı ve 2'sinde uzak metastaz vardı. Erkek cinsiyeti dışında (p= 0,021), EBER pozitifliği ile klinikopatolojik prognostik faktörler arasında istatistiksel olarak anlamlı korelasyon bulunmadı . EBV pozitifliği ile sağkalım arasında istatistiksel olarak anlamlı korelasyon bulunamadı.
Sonuç
Merkezimizde EBV ile ilişkili gastrik kanser sıklığı %5,9'dur.. EBV pozitifliği ayrıca inflamatuar hücrelerde, intestinal metaplazide ve gastrik karsinom dokusuna bitişik normal dokularda da mevcuttur.

Anahtar Kelimeler

mide kanseri , EBER , tümör mikroçevresi

Frequency of Epstein Barr Virus Positivity in Gastric Cancer and Adjacent Non-Tumoral Epithelium

https://izlik.org/JA34PC35YU

Öz

Background
Epstein-Barr virus –associated gastric cancer is one of four molecular subtypes defined by the Cancer Genome Atlas Program. Epstein-Barr virus –associated gastric cancer incidence has ethnic and geographical differences. The aims of the present study were to investigate the frequency of EBV in gastric cancer tissues and adjacent non-tumoral epithelium.
Materials and Methods
EBV positivity was assessed by chromogenic EBER-ISH in tumor tissues of 101 patients who were diagnosed with gastric carcinoma and underwent gastrectomy in our center between January 2008 and August 2023. The link between EBV incidence in gastric cancer, survival and clinicopathological prognostic factors was statistically assessed.
Results
EBV was positive in tumor tissue in 6 of 101 (%5,9) cases. In addition, positive staining was detected in intestinal metaplasia areas adjacent to the tumor in 10 cases (9.9%) and in normal gastric mucosa adjacent to the tumor in 13 cases (12.9%). All 6 cases with EBV- associated gastric cancer were male, 4 had diffuse histological type and 3 were histological grade 3, 4 had lymph node metastases and 2 had distant metastases. No statistically significant correlation was found between EBER positivity and clinicopathological prognostic factors, except for male gender (p= 0.021). There was no statistical correlation between EBV positivity and survival.
Conclusion
The frequency of EBV- associated gastric cancer was 5.9% in our center. EBV positivity is also present in inflammatory cells, intestinal metaplasia and normal tissues adjacent to gastric carcinoma tissue.

Anahtar Kelimeler

Gastric Cancer , EBER , tumor microenvironment

Etik Beyan

The study was conducted in accordance with the principles of the Declaration of Helsinki. The study was permitted by Kahramanmaraş Sütçü İmam University non-interventional clinical research ethics committee (Date: 09.11.2021, session no: 2021/36, decision no: 2).

Destekleyen Kurum

The study funded by KSU scientific research department.

Teşekkür

KSU scientific research department

Kaynakça

• 1.Sung H, Ferlay J, Siegel RL, Laversanne M,Soerjomataram I, Jemal A, et al. Global CancerStatistics 2020: GLOBOCAN Estimates of Incidence andMortality Worldwide for 36 Cancers in 185 Countries.CA Cancer J Clin. 2021;71(3):209-49.
• 2.Zur Hausen A, van Grieken NC, Meijer GA, Hermsen MA,Mast Y, Grillot-Courvalin C, et al. Distinct chromosomalabnormalities in Epstein-Barr virus-carryinggastric carcinomas tested by comparative genomichybridization. Gastroenterology. 2001;121(3):612-8.
• 3.Wu MS, Shun CT, Wu CC, Hsu TY, Lin MT, Chang MC,et al. Epstein-Barr virus-associated gastric carcinomas:relation to H. pylori infection and genetic alterations.Gastroenterology. 2000;118(6):1031-8.
• 4.van Beek J, Zur Hausen A, Klein Kranenbarg E,Jaspars EN, van de Velde CJ, Middeldorp JM, et al.EBV-positive gastric adenocarcinomas: a distinctclinicopathologic entity with a low frequency of lymphnode involvement. J Clin Oncol. 2004;22(4):664-70.
• 5.Dai C, Geng R, Wang C, Ji J, Ge J, Wu J, et al.Concordance of immune checkpoints within tumorimmune contexture and their prognostic significancein gastric cancer. Mol Oncol. 2016;10(10):1551-8.
• 6.Jácome AA, Lima EM, Kazzi AI, Castro AC, dos SantosJS. Epstein-Barr virus-positive gastric cancer: a distinctmolecular subtype of the disease? Rev Soc Bras MedTrop. 2016;49(2):150-7.
• 7.Ribeiro J, Oliveira A, Malta M, Gaiteiro C, Silva M,Soares AF, et al. Clinico-pathological characterizationof Epstein-Barr virus-associated gastric carcinomas inPortugal. World J Gastroenterol. 2017;23(40):7292-301.
• 8.Corso S, Giordano S. Molecular Classification ofGastric Cancer: A New Perspective for Treatment and Prognosis? In: D’Ugo D, Roviello F, eds. Gastric Cancer: 25 Years of R-Evolution. Springer; 2021:13-9.
• 9.Tsang CM, Yip YL, Lo KW, Deng W, To KF, Hau PM, etal. Cyclin D1 overexpression supports stable EBVinfection in nasopharyngeal epithelial cells. Proc NatlAcad Sci U S A. 2012;109(50):E3473-82.
• 10.Bass AJ, Thorsson V, Shmulevich I, Knezevic D, LazarAJ, Mezheyeuski A, et al. Comprehensive molecularcharacterization of gastric adenocarcinoma. Nature.2014;513(7517):202-9.
• 11.Özmen I, Karagöz B, Yılmaz I, Kandemir EG. Epstein-Barr virus-associated gastric carcinoma in Turkey. JClin Oncol. 2015;33(15_suppl):e15107.
• 12.Irkkan C, Balci S, Tezel GG, Ensari A. Comparison ofClinicopathologic Parameters and Survivals BetweenEpstein-Barr Virus-positive and Her2-positive GastricCancers. Appl Immunohistochem Mol Morphol.2017;25(9):609-14.
• 13.Guner G, Isik A, Karabulut E, Gedikoglu G, SokmensuerC, Akyol A. Morphological and ImmunohistochemicalEvaluation of Primary Gastric Carcinomas. ApplImmunohistochem Mol Morphol. 2018;26(10):e107-15.
• 14.Uner M, Isık A, Oztop S, Karabulut E, Demirkol-Canlı S,Akyol A. Gastric Carcinoma With Lymphoid Stroma: ACombination of Mismatch Repair Deficient MedullaryType and Epstein-Barr Virus-Associated GastricCarcinomas. Int J Surg Pathol. 2022;30(6):623-33.
• 15.Uprak TK, Akmercan A, Coşkun M, Attaallah W. Gastricmedullary carcinoma: clinicopathological featuresand prognosis—a single-center study. ANZ J Surg.2021;91(11):2425-9.
• 16.Gareayaghi N, Akkus S, Saribas S, Kirmusaoglu S,Caliskan R, Tokman HB, et al. Co-infection of Epstein-Barr Virus and Helicobacter pylori in patients withgastric cancer and duodenal ulcer. New Microbiol.2021;44(4):217-26.
• 17.Durmaz R, Aydin A, Köroglu M, Durmaz B, Ciralik H.Investigation of the relationship between Epstein-Barrvirus and ordinary gastric carcinoma using nestedpolymerase chain reaction. Acta Virol. 1998;42(6):359-63.
• 18.Hirabayashi M, Georges D, Clifford GM, de Martel C.Estimating the Global Burden of Epstein-Barr Virus-Associated Gastric Cancer: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2023;21(4):922-30.
• 19.Eskuri M, Birkman EM, Kauppila JH. Gastric cancermolecular classification and mortality based onimmunohistochemistry and in situ hybridisation.Histopathology. 2024;85(2):327-37.
• 20.Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC,Wong SS, et al. Molecular analysis of gastric canceridentifies subtypes associated with distinct clinicaloutcomes. Nat Med. 2015;21(5):449-56.
• 21.Zhang Y, Chen JN, Dong M, Wang LP, Xing XW,Shao JY. Clinical significance of spasmolyticpolypeptide-expressing metaplasia and intestinalmetaplasia in Epstein-Barr virus-associated andEpstein-Barr virus-negative gastric cancer. HumPathol. 2017;63:128-38.
• 22.Shousha S, Luqmani YA. Epstein-Barr virus ingastric carcinoma and adjacent normal gastric andduodenal mucosa. J Clin Pathol. 1994;47(8):695-8.
• 23.Herrera-Goepfert R, Akiba S, Koriyama C, CarrascalC, Guzmân-Leon S, Mizoguchi A, et al. Epstein-Barrvirus-associated gastric carcinoma: Evidence ofage-dependence in a Mexican population. WorldJ Gastroenterol. 2005;11(39):6096-103.
• 24.Truong CD, Feng W, Li W, Khoury T, Li Q, AlrawiS.Characteristics of Epstein-Barr virus-associatedgastric cancer: A study of 235 cases at acomprehensive cancer center in USA. J Exp ClinCancer Res. 2009;28:14.
• 25.Li LL, Yu AY, Zhu M, Wang J, Shi J, Pan ZL.Clinicopathological characteristics and prognosisof Epstein-Barr virus-associated gastric cancer.Arch Virol. 2024;169(5):100.
• 26.Oda K, Koda K, Takiguchi N, Nunomura M, SeikeK, Miyazaki M. Detection of Epstein-Barr virusin gastric carcinoma cells and surroundinglymphocytes. Gastric Cancer. 2003;6(3):173-8.
• 27.Wanvimonsuk S, Thitiwanichpiwong P, KeelawatS, Mutirangura A, Kitkumthorn N. Distributionof Epstein-Barr virus in normal stomach andgastric lesions in a Thai population. J Med Virol.2019;91(3):444-9.
• 28.Dursun N, Hacıhasanoğlu E, Okçu O, Paşaoğlu E,Leblebici C. Epstein-Barr virus infection in patientswith chronic gastritis without Helicobacter pyloriinfection. Turk J Gastroenterol. 2020;31(3):205-10.
• 29.Li X, Wang Y, Zhai Z, Zhao R, Gao J, Liu W, et al.Predicting the response to immunotherapyin gastric cancer by evaluating the perineuralinvasion-mediated inflammation in tumormicroenvironment. J Exp Clin Cancer Res.2023;42(1):206.
• 30.Dokanei S, Minai-Tehrani D, Moghoofei M,Rostamian M. Investigating the associationbetween Epstein-Barr virus infection and gastriccancer: A systematic review and meta-analysis.Health Sci Rep. 2024;7(3):e1976.