Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer

Annals of Surgery - Tập 270 Số 2 - Trang 309-316 - 2019
Yoon Young Choi1,2, Hyunki Kim3, Su‐Jin Shin4, Ha Yan Kim5, Jinae Lee5, Han‐Kwang Yang6, Woo Ho Kim7, Young‐Woo Kim8, Myeong‐Cherl Kook8, Young Kyu Park9, Hyung‐Ho Kim10, Hye Seung Lee11, Kyung Hee Lee12, Mi Jin Gu13, Seung Ho Choi14, Soon Won Hong3, Jong Won Kim15, Woo Jin Hyung1, Sung Hoon Noh16,1, Jae‐Ho Cheong16,17,1,2
1Department of Surgery, Yonsei University Health System, Seoul, South Korea
2Yonsei Biomedical Research Institute, Seoul, South Korea
3Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
4Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea
5Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea
6Department of Surgery and Cancer Research Institute, Seoul, South Korea
7Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea
8Center for Gastric Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
9Department of Surgery, Chonnam National University Hwasun Hospital, Jeonnam, South Korea
10Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
11Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, South Korea
12Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
13Department of Pathology, Yeungnam University College of Medicine, Daegu, South Korea
14Department of Surgery, Gangnam Severance Hospital, Seoul, South Korea
15Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea
16Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
17Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.

Tóm tắt

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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Annals of Surgery

Tập 270 Số 2

309-316

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