Review

Vol. 117: Issue 6 - December 2025

The clinical impact of precise assessment of predictive biomarkers in gastroesophageal cancer: focus on the PD-L1 combined positive score (CPS) and tumor area positivity (TAP) systems

Authors

Alessandro Gambella , Valentina Angerilli , Federica Grillo , Filippo Pietrantonio , Alessandro Vanoli , Paola Parente , Paola Cassoni , Maria Cristina Macciomei , Alessandro Caputo , Francesco Giuseppe Carbone , Chiara Taffon , Carla Giordano , Luca Mastracci , Matteo Fassan

Key words: gastro-esophageal cancer, immune checkpoint inhibitors, clinical trials, Digital pathology, Artificial intelligence
DOI: 10.32074/1591-951X-1759
Publication Date: 2026-02-06

Abstract

Accurate assessment of PD-L1 expression is crucial for therapeutic decision-making in esophageal, esophago-gastric junction, and gastric cancers, where immune checkpoint inhibitors have become integral to first-line treatment in selected patients. This review provides an updated, practice-oriented summary on PD-L1 immunohistochemistry evaluation, with emphasis on the emerging Tumor Area Positivity (TAP) scoring system together with established Combined Positive Score (CPS) and Tumor Proportion Score. First, we examine the clinical relevance and use in clinical trials of each scoring method, and the pre-analytical and analytical variables influencing PD-L1 interpretation. Then, we address advantages and disadvantages of each scoring system, including a thorough analysis and pictorial interpretation guide of the recently introduced TAP score. Indeed, thanks to a visual-estimation-based assessment of PD-L1 expression, TAP has improved reproducibility and reduced scoring time, but large-scale validation is ongoing and certain interpretive challenges remain. Finally, we propose a standardized reporting template to enhance consistency in diagnostic practice, together with our perspective on future improvements and challenges of PD-L1 assessment.

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Authors

Alessandro Gambella - Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy. https://orcid.org/0000-0001-7826-002X

Valentina Angerilli - Surgical Pathology Unit, ULSS2 Marca Trevigiana, Treviso, Italy

Federica Grillo - Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy; IRCCS San Martino Policlinic Hospital, Genoa, Italy.

Filippo Pietrantonio - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Alessandro Vanoli - Department of Molecular Medicine, University of Pavia, Pavia, Italy; Anatomic Pathology, IRCCS San Matteo Hospital Foundation, Pavia, Italy.

Paola Parente - UOC Anatomia Patologica Azienda Ospedaliera Universitaria Ospedali Riuniti di Foggia, Foggia, Italy. https://orcid.org/0000-0003-0591-6723

Paola Cassoni - Città della Salute e della Scienza University Hospital, Turin; Pathology Unit, Department of Medical Sciences, University of Turin, Turin

Maria Cristina Macciomei - Azienda Ospedaliera San Camillo Forlanini, Roma

Alessandro Caputo - Department of Pathology, University Hospital of Salerno, Salerno, Italy; Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Baronissi, Italy https://orcid.org/0000-0001-5139-3869

Francesco Giuseppe Carbone - Department of Laboratory Medicine - Pathology Unit, Santa Chiara Hospital, APSS, Trento, Italy.

Chiara Taffon - Pathology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy

Carla Giordano - Department of Radiological, Oncological and Pathological Sciences, Sapienza, University of Rome, Rome, Italy

Luca Mastracci - Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy; IRCCS San Martino Policlinic Hospital, Genoa, Italy. https://orcid.org/0000-0003-0193-5281

Matteo Fassan - Department of Medicine (DIMED), University of Padua, Padua, Italy; Veneto Institute of Oncology (IOV.IRCCS), Padua, Italy.

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Copyright

Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Gambella, A., Angerilli, V., Grillo, F., Pietrantonio, F., Vanoli, A., Parente, P., Cassoni, P., Macciomei, M. C., Caputo, A., Carbone, F. G., Taffon, C., Giordano, C., Mastracci, L., & Fassan, M. (2026). The clinical impact of precise assessment of predictive biomarkers in gastroesophageal cancer: focus on the PD-L1 combined positive score (CPS) and tumor area positivity (TAP) systems. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(6). https://doi.org/10.32074/1591-951X-1759
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