Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer

Abstract Purpose Programmed cell death ligand 1 (PD-L1) expression in advanced gastric cancer (AGC) exhibits spatial heterogeneity, which may lead to sampling bias during biopsies. Although multiple biopsies are believed to improve the accuracy of PD-L1 assessment, the optimal number of specimens re...

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Main Authors: Taro Mizuno, Yukiya Narita, Yasunobu Ishizuka, Tomoki Sakakida, Kazunori Honda, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Masashi Ando, Masahiro Tajika, Kei Muro
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Journal of Cancer Research and Clinical Oncology
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Online Access:https://doi.org/10.1007/s00432-025-06255-1
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author Taro Mizuno
Yukiya Narita
Yasunobu Ishizuka
Tomoki Sakakida
Kazunori Honda
Toshiki Masuishi
Hiroya Taniguchi
Shigenori Kadowaki
Masashi Ando
Masahiro Tajika
Kei Muro
author_facet Taro Mizuno
Yukiya Narita
Yasunobu Ishizuka
Tomoki Sakakida
Kazunori Honda
Toshiki Masuishi
Hiroya Taniguchi
Shigenori Kadowaki
Masashi Ando
Masahiro Tajika
Kei Muro
author_sort Taro Mizuno
collection DOAJ
description Abstract Purpose Programmed cell death ligand 1 (PD-L1) expression in advanced gastric cancer (AGC) exhibits spatial heterogeneity, which may lead to sampling bias during biopsies. Although multiple biopsies are believed to improve the accuracy of PD-L1 assessment, the optimal number of specimens remains uncertain. This study investigated the relationship between PD-L1 expression and biopsy specimen count in AGC. Methods We retrospectively analyzed 110 patients with AGC who underwent first-line chemotherapy and had PD-L1 combined positive scores (CPS) assessed using the 28-8 pharmDx assay. Associations between CPS and biopsy specimen count were evaluated using chi-square or Fisher’s exact test. In a subgroup of 70 human epidermal growth factor receptor 2 (HER2)-negative patients treated with first-line nivolumab plus chemotherapy, survival outcomes were analyzed based on CPS status. Results PD-L1 CPS ≥ 5 was identified in 79 patients (71.8%). The proportion of patients with CPS ≥ 5 was significantly higher in those with ≥ 5 biopsy specimens than in those with ≤ 4 (77.5% vs. 56.7%, P = 0.03). This trend was even more pronounced in HER2-negative patients (83.6% vs. 54.5%, P < 0.01) and in those with macroscopic type 2 tumors (91.3% vs. 33.3%, P < 0.01). However, no significant differences in progression-free or overall survival were found based on CPS status, regardless of biopsy count. Conclusion Obtaining at least five biopsy specimens enhances the detection of PD-L1 CPS ≥ 5, particularly in HER2-negative or well-circumscribed nodular AGC, potentially improving the accuracy of PD-L1 evaluation. Nevertheless, survival outcomes were unaffected, highlighting the limited predictive value of CPS.
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spelling doaj-art-b416c7d5fedd4a4b89619987e94c572d2025-08-20T03:04:18ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-07-0115171710.1007/s00432-025-06255-1Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancerTaro Mizuno0Yukiya Narita1Yasunobu Ishizuka2Tomoki Sakakida3Kazunori Honda4Toshiki Masuishi5Hiroya Taniguchi6Shigenori Kadowaki7Masashi Ando8Masahiro Tajika9Kei Muro10Department of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalDepartment of Endoscopy, Aichi Cancer Center HospitalDepartment of Clinical Oncology, Aichi Cancer Center HospitalAbstract Purpose Programmed cell death ligand 1 (PD-L1) expression in advanced gastric cancer (AGC) exhibits spatial heterogeneity, which may lead to sampling bias during biopsies. Although multiple biopsies are believed to improve the accuracy of PD-L1 assessment, the optimal number of specimens remains uncertain. This study investigated the relationship between PD-L1 expression and biopsy specimen count in AGC. Methods We retrospectively analyzed 110 patients with AGC who underwent first-line chemotherapy and had PD-L1 combined positive scores (CPS) assessed using the 28-8 pharmDx assay. Associations between CPS and biopsy specimen count were evaluated using chi-square or Fisher’s exact test. In a subgroup of 70 human epidermal growth factor receptor 2 (HER2)-negative patients treated with first-line nivolumab plus chemotherapy, survival outcomes were analyzed based on CPS status. Results PD-L1 CPS ≥ 5 was identified in 79 patients (71.8%). The proportion of patients with CPS ≥ 5 was significantly higher in those with ≥ 5 biopsy specimens than in those with ≤ 4 (77.5% vs. 56.7%, P = 0.03). This trend was even more pronounced in HER2-negative patients (83.6% vs. 54.5%, P < 0.01) and in those with macroscopic type 2 tumors (91.3% vs. 33.3%, P < 0.01). However, no significant differences in progression-free or overall survival were found based on CPS status, regardless of biopsy count. Conclusion Obtaining at least five biopsy specimens enhances the detection of PD-L1 CPS ≥ 5, particularly in HER2-negative or well-circumscribed nodular AGC, potentially improving the accuracy of PD-L1 evaluation. Nevertheless, survival outcomes were unaffected, highlighting the limited predictive value of CPS.https://doi.org/10.1007/s00432-025-06255-1Advanced gastric cancerPD-L1 CPSBiopsy specimen count
spellingShingle Taro Mizuno
Yukiya Narita
Yasunobu Ishizuka
Tomoki Sakakida
Kazunori Honda
Toshiki Masuishi
Hiroya Taniguchi
Shigenori Kadowaki
Masashi Ando
Masahiro Tajika
Kei Muro
Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
Journal of Cancer Research and Clinical Oncology
Advanced gastric cancer
PD-L1 CPS
Biopsy specimen count
title Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
title_full Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
title_fullStr Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
title_full_unstemmed Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
title_short Relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
title_sort relationship between programmed cell death ligand 1 expression and the number of biopsy specimens in advanced gastric cancer
topic Advanced gastric cancer
PD-L1 CPS
Biopsy specimen count
url https://doi.org/10.1007/s00432-025-06255-1
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