Cancer Res Treat.  2019 Apr;51(2):819-831. 10.4143/crt.2018.331.

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

• Kim MH
• Zhang X
• Jung M
• Jung I
• Park HS
• Beom SH
• Kim HS
• Rha SY
• Kim H
• Choi YY
• Son T
• Kim HI
• Cheong JH
• Hyung WJ
• Noh SH
• Chung HC

• KMID: 2464427
• DOI: http://doi.org/10.4143/crt.2018.331

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 gastrectomywith orwithout 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.

Keyword

Biomarkers; Stomach neoplasms; Prognosis; Thymidylate synthase; PD-L1; ERCC1

MeSH Terms

Biomarkers*
Capecitabine
Chemotherapy, Adjuvant
Disease-Free Survival
DNA Repair
Humans
Immunohistochemistry*
Prognosis
Prospective Studies*
Recurrence
Stomach Neoplasms*
Thymidylate Synthase
Biomarkers
Capecitabine
Thymidylate Synthase

Figure

• 

  Fig. 1. Representative images of positive and negative staining results for TS, ERCC1, and PD-L1 in the primary gastric tumors. TS, thymidylate synthase; ERCC1, excision repair cross-complementation group 1; PD-L1, programmed death-ligand 1. Scale bars=100 μm.

• 

  Fig. 2. Kaplan-Meier curves for DFS and OS according to TS, ERCC1, and PD-L1 expression among all 139 patients. The DFS and OS outcomes were compared using the log-rank test. DFS, disease-free survival; OS, overall survival; TS, thymidylate synthase; ERCC1, excision repair cross-complementation group 1; PD-L1, programmed death-ligand 1.

• 

  Fig. 3. Kaplan-Meier curves for DFS and OS according to TS, ERCC1, and PD-L1 expression in 66 patients who received adjuvant chemotherapy. The DFS and OS outcomes were compared using the log-rank test. DFS, disease-free survival; OS, overal survival; TS, thymidylate synthase; ERCC1, excision repair cross-complementation group 1; PD-L1, programmed death-ligand 1.

• 

  Fig. 4. Kaplan-Meier curves for DFS and OS according to TS, ERCC1, and PD-L1 expression in 73 patients who only underwent surgery. The DFS and OS outcomes were compared using the log-rank test. DFS, disease-free survival; OS, overall survival; TS, thymidylate synthase; ERCC1, excision repair cross-complementation group 1; PD-L1, programmed death-ligand 1.

Reference

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