Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study

Yoon Young Choi, Hyunki Kim, Su Jin Shin, Ha Yan Kim, Jinae Lee, Han Kwang Yang, Woo Ho Kim, Young Woo Kim, Myeong Cherl Kook, Young Kyu Park, Hyung Ho Kim, Hye Seung Lee, Kyung Hee Lee, Mi Jin Gu, Seung Ho Choi, Soonwon Hong, Jong Won Kim, Woo Jin Hyung, Sung Hoon Noh, Jae Ho Cheong

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126 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalAnnals of surgery
Issue number2
Publication statusPublished - 2019 Aug 1

Bibliographical note

Funding Information:
Funding: This research was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1020390, 1320360), and by a faculty research grant from the Yonsei Univer-sity College of Medicine (6–2007–0095, 6–2008–0193).

Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Surgery


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