Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study
- Authors
- Choi, Y.Y.; Kim, H.; Shin, S.-J.; Kim, H.; Lee, J.; Yang, H.-K.; Kim, W.H.; Kim, Y.-W.; Kook, M.-C.; Park, Y.K.; Kim, H.; Lee, H.S.; Lee, K.H.; Gu, M.J.; Choi, S.H.; Hong, S.; Kim, J.W.; Hyung, W.J.; Noh, S.H.; Cheong, J.-H.
- Issue Date
- Aug-2019
- Publisher
- NLM (Medline)
- Keywords
- biomarker; chemotherapy; gastric cancer; microsatellite instability; programmed cell death ligand 1
- Citation
- Annals of surgery, v.270, no.2, pp 309 - 316
- Pages
- 8
- Journal Title
- Annals of surgery
- Volume
- 270
- Number
- 2
- Start Page
- 309
- End Page
- 316
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/36494
- DOI
- 10.1097/SLA.0000000000002803
- ISSN
- 1528-1140
1528-1140
- Abstract
- OBJECTIVE: We investigated microsatellite instability (MSI) status and programed cell death ligand 1 (PD-L1) expression as predictors of prognosis and responsiveness to chemotherapy for stage II/III gastric cancer. BACKGROUND: The clinical implications of MSI status and PD-L1 expression in gastric cancer have not been well-elucidated. METHODS: Tumor specimens and clinical information were collected from patients enrolled in the CLASSIC trial-a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. Five quasi-monomorphic mononucleotide markers were used to assess tumor MSI status. PD-L1 expressions of tumor and stromal immune cells were evaluated using immunohistochemistry. RESULTS: Of 592 patients, 40 (6.8%) had MSI-high (MSI-H) tumors. Among 582 patients available for immunohistochemistry evaluation, PD-L1 was positive in tumor cells (tPD-L1) of 16 patients (2.7%) and stromal immune cells (sPD-L1) of 165 patients (28.4%). Multivariable analysis of disease-free survival (DFS) showed that MSI-H and sPD-L1-positivity were independent prognostic factors [hazard ratio 0.301 (0.123-0.736), 0.714 (0.514-0.991); P = 0.008, 0.044), as were receiving chemotherapy, age, tumor grade, and TNM stage. Although adjuvant chemotherapy improved DFS in the microsatellite-stable (MSS) group (5-year DFS: 66.8% vs 54.1%; P = 0.002); no benefit was observed in the MSI-H group (5-year DFS: 83.9% vs 85.7%; P = 0.931). In the MSS group, sPD-L1-negative patients, but not sPD-L1-positive patients, had significant survival benefit from adjuvant chemotherapy compared with surgery only (5-year DFS: 66.1% vs 50.7%; P = 0.001). CONCLUSION: MSI status and PD-L1 expression are clinically actionable biomarkers for stratifying patients and predicting benefit from adjuvant chemotherapy after D2 gastrectomy for stage II/III gastric cancer.
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