Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer  

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作  者:Carlos A Castaneda Miluska Castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa 

机构地区:[1]Faculty of Health Sciences,Universidad Cientifica del Sur,Lima 15038,Peru [2]GECO PERU,Grupo de Estudios Clinicos Oncologicos del Peru,Lima 15038,Peru [3]Department of Research,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [4]Faculty of Human Medicine,Universidad Ricardo Palma,Lima 15039,Peru [5]Department of Medicine,Surgical Pathology&Cytopathology Unit,University of Padua,Padua 35121,Italy [6]Department of Translational Molecular Pathology,The University of Texas MD Anderson Cancer Center,Houston,TX 77030,United States [7]Department of Abdominal Surgery,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [8]Department of Pathology,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [9]Department of Medical Specialties,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [10]Department of Pathology,Instituto Regional de Enfermedades Neoplasicas del Norte,Trujillo 13001,Peru [11]Faculty of Human Medicine,Universidad Privada Antenor Orrego,Trujillo 13008,Peru [12]Department of Surgery,Instituto Regional de Enfermedades Neoplasicas del Sur,Arequipa 04002,Peru [13]Department of Medical Oncology,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [14]Department of Epidemiology,Instituto Nacional de Enfermedades Neoplasicas,Lima 15038,Peru [15]Unidad de Investigación Básica y Traslacional,Oncosalud-AUNA,Lima 15038,Peru [16]Faculty of Medicine,Universidad San Martin de Porres,Lima 15008,Peru

出  处:《World Journal of Gastrointestinal Oncology》2024年第6期2487-2503,共17页世界胃肠肿瘤学杂志(英文版)(电子版)

基  金:Supported by Ministerio de la Produccion de Peru,No.317-PNICP-EC-2014,and No.430-PNICP-PIAP-2014;Consejo Nacional de Ciencia Tecnologia e Innovacion Tecnologica,No.196-2015-FONDECYT,No.197-2015-FONDECYT,and No.204-2015-FONDECYT.

摘  要:BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关 键 词:LYMPHOCYTES MACROPHAGES Gastric cancer Helicobacter pylori HER2 Mismatch repair 

分 类 号:R735.2[医药卫生—肿瘤]

 

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