Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression.

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gastric Cancer Pub Date : 2025-03-01 Epub Date: 2025-01-05 DOI:10.1007/s10120-024-01578-3
Carolina Martínez-Ciarpaglini, Rita Barros, Carmelo Caballero, Hugo Boggino, Lorena Alarcón-Molero, Bárbara Peleteiro, Erika Ruiz-García, Edith Fernandez-Figueroa, Roberto Herrera-Goepfert, Consuelo Díaz-Romero, Rui Ferreira, Tessa S Groen-van Schooten, Cinthia Gauna, Rita Pereira, Daniel Cantero, Horacio Lezcano, Federico Esteso, Juan O Connor, Arnoldo Riquelme, Gareth I Owen, Marcelo Garrido, Juan Carlos Roa, Fiorella Ruiz-Pace, Ana Vivancos, Marc Diez-García, Maria Alsina, Judit Matito, Agatha Martin, Marina Gómez, Ester Castillo, Maria Vila, João Santos-Antunes, Andreia Costa, Florian Lordick, Judith Farrés, Brenda Palomar-De Lucas, Manuel Cabeza-Segura, Rosanna Villagrasa, Elena Jimenez-Martí, Ana Miralles-Marco, Rodrigo Dienstmann, Sarah Derks, Ceu Figueiredo, Andrés Cervantes, Fátima Carneiro, Tania Fleitas-Kanonnikoff
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引用次数: 0

Abstract

Introduction: Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Material and methods: Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries. Formalin-fixed paraffin-embedded primary tumour endoscopic biopsy samples were collected and submitted for central morphological and immunohistochemical characterization and TP53 molecular assessment and Helicobacter pylori infection.

Results: A total of 259 patients were included in the study: 137 (53%) from LATAM and 122 (47%) from Europe. Significant biological differences were detected between European and LATAM patients. Low representation of chromosomal instability (CIN) and HER2 positive cases were found in LATAM. MUC6 and PD-L1 were more frequently overexpressed in European cases, showing a significant correlation across the entire study population, with this association being especially pronounced in MMRdeficient cases. Both TP53 mutation by next-generation sequencing and p53 immunohistochemical aberrant pattern were linked with features associated with chromosomal instability. No regional differences were observed in H. pylori prevalence or abundance, indicating that the afore mentioned variations cannot be attributed to this factor.

Conclusion: Our findings underscore a need for region-specific approaches in gastroesophageal cancer diagnosis and treatment. MUC6 emerges as a putative immune regulator that needs further investigation. Research tailored to the unique biological profiles in different global regions is crucial to effectively address the observed disparities.

欧洲和拉丁美洲人群胃癌的综合组织病理学分析揭示了PDL1、HER2、p53和MUC6表达的差异。
胃癌(GC)负担目前正在演变,与复杂的行为、环境和遗传风险因素相关的区域差异。LEGACy研究是一项由Horizon 2020资助的多机构研究项目,旨在提供欧洲和拉丁美洲国家胃食管癌肿瘤生物学特征的综合数据。材料和方法:Treatment-naïve前瞻性招募七个欧洲和拉丁美洲国家的晚期胃食管腺癌患者。收集经福尔马林固定石蜡包埋的原发性肿瘤内镜活检标本,进行中心形态学和免疫组织化学鉴定、TP53分子评估和幽门螺杆菌感染。结果:共有259例患者纳入研究:137例(53%)来自拉丁美洲,122例(47%)来自欧洲。在欧洲和拉丁美洲患者之间发现了显著的生物学差异。在LATAM中发现染色体不稳定性(CIN)和HER2阳性病例的低代表性。MUC6和PD-L1在欧洲病例中更频繁地过表达,在整个研究人群中显示出显著的相关性,这种相关性在mmr缺陷病例中尤为明显。新一代测序的TP53突变和p53免疫组织化学异常模式都与染色体不稳定性相关的特征有关。在幽门螺杆菌患病率或丰度方面没有观察到区域差异,表明上述差异不能归因于这一因素。结论:我们的研究结果强调了在胃食管癌的诊断和治疗中需要有区域特异性的方法。MUC6被认为是一种免疫调节因子,需要进一步研究。针对全球不同区域独特的生物概况进行研究,对于有效解决所观察到的差异至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
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