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

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Abstract

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.

Original languageEnglish
Pages (from-to)819-831
Number of pages13
JournalCancer Research and Treatment
Volume51
Issue number2
DOIs
Publication statusPublished - 2019 Jan 1

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, M. H., Zhang, X., Jung, M., Jung, I., Park, H. S., Beom, S. H., Kim, H. S., Rha, S. Y., Kim, H., Choi, Y. Y., Son, T., Kim, H. I., Cheong, J. H., Hyung, W. J., Noh, S. H., & Chung, H. C. (2019). Immunohistochemistry biomarkers predict survival in stage II/III gastric cancer patients: From a prospective clinical trial. Cancer Research and Treatment, 51(2), 819-831. https://doi.org/10.4143/crt.2018.331