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Introduction <p>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.</p> Material and methods <p>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 <i>Helicobacter pylori</i> infection.</p> Results <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.</p> Conclusion <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.</p>

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

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  • 发表日期：

    2025年1月5日

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  • 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

摘要

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.