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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Material and methods<\/jats:title>\n            <jats:p>Treatment-na\u00efve 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 <jats:italic>Helicobacter pylori<\/jats:italic> infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10120-024-01578-3","type":"journal-article","created":{"date-parts":[[2025,1,5]],"date-time":"2025-01-05T12:35:17Z","timestamp":1736080517000},"page":"160-173","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression"],"prefix":"10.1007","volume":"28","author":[{"given":"Carolina","family":"Mart\u00ednez-Ciarpaglini","sequence":"first","affiliation":[]},{"given":"Rita","family":"Barros","sequence":"additional","affiliation":[]},{"given":"Carmelo","family":"Caballero","sequence":"additional","affiliation":[]},{"given":"Hugo","family":"Boggino","sequence":"additional","affiliation":[]},{"given":"Lorena","family":"Alarc\u00f3n-Molero","sequence":"additional","affiliation":[]},{"given":"B\u00e1rbara","family":"Peleteiro","sequence":"additional","affiliation":[]},{"given":"Erika","family":"Ruiz-Garc\u00eda","sequence":"additional","affiliation":[]},{"given":"Edith","family":"Fernandez-Figueroa","sequence":"additional","affiliation":[]},{"given":"Roberto","family":"Herrera-Goepfert","sequence":"additional","affiliation":[]},{"given":"Consuelo","family":"D\u00edaz-Romero","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Tessa S.","family":"Groen-van Schooten","sequence":"additional","affiliation":[]},{"given":"Cinthia","family":"Gauna","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Cantero","sequence":"additional","affiliation":[]},{"given":"Horacio","family":"Lezcano","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Esteso","sequence":"additional","affiliation":[]},{"given":"Juan","family":"O\u00b4Connor","sequence":"additional","affiliation":[]},{"given":"Arnoldo","family":"Riquelme","sequence":"additional","affiliation":[]},{"given":"Gareth I.","family":"Owen","sequence":"additional","affiliation":[]},{"given":"Marcelo","family":"Garrido","sequence":"additional","affiliation":[]},{"given":"Juan Carlos","family":"Roa","sequence":"additional","affiliation":[]},{"given":"Fiorella","family":"Ruiz-Pace","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Vivancos","sequence":"additional","affiliation":[]},{"given":"Marc","family":"Diez-Garc\u00eda","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Alsina","sequence":"additional","affiliation":[]},{"given":"Judit","family":"Matito","sequence":"additional","affiliation":[]},{"given":"Agatha","family":"Martin","sequence":"additional","affiliation":[]},{"given":"Marina","family":"G\u00f3mez","sequence":"additional","affiliation":[]},{"given":"Ester","family":"Castillo","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Vila","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Santos-Antunes","sequence":"additional","affiliation":[]},{"given":"Andreia","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[]},{"given":"Judith","family":"Farr\u00e9s","sequence":"additional","affiliation":[]},{"given":"Brenda","family":"Palomar-De Lucas","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Cabeza-Segura","sequence":"additional","affiliation":[]},{"given":"Rosanna","family":"Villagrasa","sequence":"additional","affiliation":[]},{"given":"Elena","family":"Jimenez-Mart\u00ed","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Miralles-Marco","sequence":"additional","affiliation":[]},{"given":"Rodrigo","family":"Dienstmann","sequence":"additional","affiliation":[]},{"given":"Sarah","family":"Derks","sequence":"additional","affiliation":[]},{"given":"Ceu","family":"Figueiredo","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9s","family":"Cervantes","sequence":"additional","affiliation":[]},{"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-9082","authenticated-orcid":false,"given":"Tania","family":"Fleitas-Kanonnikoff","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,1,5]]},"reference":[{"issue":"3","key":"1578_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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Institutional research funding from Merck. FL Dr. Lordick reports institutional grants from: Astra Zeneca, Beigene, BMS, Daiichi Sankyo and Gilead, and personal fees from: Amgen, ArtTempi. Astellas, Astra Zeneca, Bayer, Biontech, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Gilead, Elsevier, Incyte, Medscape, MedUpdate, Merck Serono, MSD, PAGE, Roche, Servier, StreamedUp!, VJ Oncology, all outside the submitted work.\u00a0Dr. Fleitas discloses advisory roles honoraria from Amgen, AstraZeneca, Beigene, BMS and MSD. Institutional research funding from Gilead. Speaker honoraria from Amgen, Servier, BMS, MSD, Lilly, Roche, Bayer. The other authors has no conflict of interests to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study has been conducted according to the principles of the Declaration of Helsinki (Fortaleza, Brazil, October 2013), following the Medical Research Involving Human Subjects Act and Good Clinical Practice standards. The study can be found under ClinicalTrials.gov Identifier: NCT04015466, July 11, 2019. The study protocol has been approved by the ethics committee of all patient-recruiting centers: the ethics committee of University Clinical Hospital of Valencia, Spain (reference number 2018\/205), the institutional review board of VU University Medical Center Amsterdam (reference number 2019.355. NL 69480.02919), the ethics committee of Instituto de Previsi\u00f3n Social, Asuncion-Paraguay (reference number CA N\u00b011\u2013020\/19), the ethical research committee of Instituto Alexander Fleming, Buenos Aires Argentina (Resolution July 25th, 2019, for LEGACy study 1 and 2 and October 3rd, 2019 for LEGACy study 3); the ethical committee of Instituto Nacional de Cancerolog\u00eda (INCAN, M\u00e9xico (reference number INCAN\/CEI\/0486\/19). The ethics committee of the University Center of Sao Joao and Medicine Faculty of Porto University, Portugal (reference 100\/019), the scientific ethical Committee Pontificia University of Chili, reference 180806007, and the Drug research ethics committee of Valld\u2019Hebron University Hospital, Barcelona, Spain with references PR (AG)387\/2019 approved on October 29th, 2019 for LEGACy study 1, PR (AG)388\/2019 approved in December 13th 2019 for LEGACy study 2 and PR (AG)419\/2019 approved in January 30th, 2020 for Legacy study 3 respectively. All participants provided written informed consent before study enrolment. Each data-contributing partner has undergone online ethical and data training before the beginning of data collection and has managed access to the data of their center through this security system. Inside this system, a patient ID generator has generated a unique code for each participating patient to maintain data privacy.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}