ESMO open · 2025
Critical insights on real-life PD-L1 histopathological workflow and assessment in esophageal, esophagogastric junction, and gastric carcinoma in Italy.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gambella A, Grillo F, Parente P, Vanoli A, Caputo A, Paudice M, Angerilli V, Castri F, Pastorino A, Fassan M, Mastracci L, RELIABL Study Group
Аннотация
BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have improved survival in locally advanced and metastatic esophageal, esophagogastric junction, and gastric carcinoma (GEC). Patient selection for ICI-treatment relies on PD-L1 protein expression assessment via immunohistochemistry (IHC). This study aimed to evaluate the real-world assessment of PD-L1 IHC results compared with clinical trial data.
PATIENTS AND METHODS: This multicentric, real-world retrospective study analyzed PD-L1 IHC data from 28 Italian pathology centers of GEC cases diagnosed between October 2023 and September 2024. The study documented PD-L1 expression distribution via combined positive (CPS), tumor proportion (TPS), and tumor area positivity (TAP) scores, and investigated the impact of several factors on IHC results.
RESULTS: We collected 1936 cases: 1802 adenocarcinomas (ADCA), 131 squamous carcinomas (SCC), and 3 carcinomas of non-specific histotype. Most institutions reported CPS and TPS data, whereas a minority used TAP. Overall, CPS, TPS, and TAP scores were in line with the data in literature and clinical trials for both ADCA and SCC, but inter-institutional heterogeneity was observed as represented by CPS ≥1 ADCA cases (range among institutions: 43.6%-100%). Inter-institutional heterogeneity was significantly associated with several variables, including (i) PD-L1 IHC case workload, with lower workload centers reporting more CPS ≥1 cases on average, and (ii) PD-L1 clone, with the 22C3 clone showing higher CPS scores than the SP263 clone. Tissue block aging was also significantly associated with a lower PD-L1 score, with a critical time window at 24-60 months.
CONCLUSIONS: This study confirms the alignment of GEC PD-L1 expression in Italian real-world practice with clinical trials. Inter-institutional variability and the significant influence of preanalytical factors, particularly tissue aging and PD-L1 clone, highlight important challenges in routine PD-L1 testing. Addressing these issues is crucial to enhance the reliability of PD-L1 IHC assessment and ensure optimal patient selection for ICIs in GEC.
PATIENTS AND METHODS: This multicentric, real-world retrospective study analyzed PD-L1 IHC data from 28 Italian pathology centers of GEC cases diagnosed between October 2023 and September 2024. The study documented PD-L1 expression distribution via combined positive (CPS), tumor proportion (TPS), and tumor area positivity (TAP) scores, and investigated the impact of several factors on IHC results.
RESULTS: We collected 1936 cases: 1802 adenocarcinomas (ADCA), 131 squamous carcinomas (SCC), and 3 carcinomas of non-specific histotype. Most institutions reported CPS and TPS data, whereas a minority used TAP. Overall, CPS, TPS, and TAP scores were in line with the data in literature and clinical trials for both ADCA and SCC, but inter-institutional heterogeneity was observed as represented by CPS ≥1 ADCA cases (range among institutions: 43.6%-100%). Inter-institutional heterogeneity was significantly associated with several variables, including (i) PD-L1 IHC case workload, with lower workload centers reporting more CPS ≥1 cases on average, and (ii) PD-L1 clone, with the 22C3 clone showing higher CPS scores than the SP263 clone. Tissue block aging was also significantly associated with a lower PD-L1 score, with a critical time window at 24-60 months.
CONCLUSIONS: This study confirms the alignment of GEC PD-L1 expression in Italian real-world practice with clinical trials. Inter-institutional variability and the significant influence of preanalytical factors, particularly tissue aging and PD-L1 clone, highlight important challenges in routine PD-L1 testing. Addressing these issues is crucial to enhance the reliability of PD-L1 IHC assessment and ensure optimal patient selection for ICIs in GEC.