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
2018May ; 128 ( 4 ) :.
PMID : 29727332
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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 -
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.
Bio maker, chemotherapy, gastric cancer, microsatelite instability, programmed cell death ligand 1 (PD-L1)
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