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

 Choi, Yoon Young  ;  Kim, Hyunki  ;  Shin, Su-Jin  ;  Kim, Ha Yan  ;  Lee, Jinae  ;  Yang, Han-Kwang  ;  Kim, Woo Ho  ;  Kim, Young-Woo  ;  Kook, Myeong-Cherl  ;  Park, Young Kyu  ;  Kim, Hyung-Ho  ;  Lee, Hye Seung  ;  Lee, Kyung Hee  ;  Gu, Mi Jin  ;  Choi, Seung Ho  ;  Hong, SoonWon  ;  Kim, Jong Won  ;  Hyung, Woo Jin  ;  Noh, Sung Hoon  ;  Cheong, Jae-Ho 
 ANNALS OF SURGERY, Vol.270(2) : 309-316, 2019 
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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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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Lee, Jinae(이진애)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Choi, Seung Ho(최승호) ORCID logo https://orcid.org/0000-0002-9872-3594
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
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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