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Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial

 Min Hwan Kim  ;  Xianglan Zhang  ;  Minkyu Jung  ;  Inkyung Jung  ;  Hyung Soon Park  ;  Seung-Hoon Beom  ;  Hyo Song Kim  ;  Sun Young Rha  ;  Hyunki Kim  ;  Yoon Young Choi  ;  Taeil Son  ;  Hyoung-Il Kim  ;  Jae-Ho Cheong  ;  Woo Jin Hyung  ;  Sung Hoon Noh  ;  Hyun Cheol Chung 
 Cancer Research and Treatment, Vol.51(2) : 819-831, 2019 
Journal Title
 Cancer Research and Treatment 
Issue Date
Adult ; Aged ; B7-H1 Antigen/metabolism ; Biomarkers, Tumor* ; Clinical Trials, Phase III as Topic ; Combined Modality Therapy ; DNA-Binding Proteins/metabolism ; Endonucleases/metabolism ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multicenter Studies as Topic ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Randomized Controlled Trials as Topic ; Stomach Neoplasms/metabolism* ; Stomach Neoplasms/mortality* ; Stomach Neoplasms/pathology ; Stomach Neoplasms/therapy
Biomarkers ; ERCC1 ; PD-L1 ; Prognosis ; Stomach neoplasms ; Thymidylate synthase
PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. Materials and Methods: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomy with or without adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Kim, Min Hwan(김민환) ORCID logo https://orcid.org/0000-0002-1595-6342
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hyoung Il(김형일) ORCID logo https://orcid.org/0000-0002-6134-4523
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Hyung Soon(박형순)
Beom, Seung Hoon(범승훈) ORCID logo https://orcid.org/0000-0001-7036-3753
Son, Tae Il(손태일) ORCID logo https://orcid.org/0000-0002-0327-5224
Zhang, Xiang Lan(장향란)
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Choi, Yoon Young(최윤영) ORCID logo https://orcid.org/0000-0002-2179-7851
Hyung, Woo Jin(형우진) ORCID logo https://orcid.org/0000-0002-8593-9214
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