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

被引：210

作者：

Choi, Yoon Young ^{[1
,2
]}

Kim, Hyunki ^{[3
]}

Shin, Su-Jin ^{[4
]}

Kim, Ha Yan ^{[5
]}

Lee, Jinae ^{[5
]}

Yang, Han-Kwang ^{[6
,7
]}

Kim, Woo Ho ^{[8
]}

Kim, Young-Woo ^{[9
]}

Kook, Myeong-Cherl ^{[9
]}

Park, Young Kyu ^{[10
]}

Kim, Hyung-Ho ^{[11
]}

Lee, Hye Seung ^{[12
]}

Lee, Kyung Hee ^{[13
]}

Gu, Mi Jin ^{[14
]}

Choi, Seung Ho ^{[15
]}

Hong, SoonWon ^{[16
]}

Kim, Jong Won ^{[17
]}

Hyung, Woo Jin ^{[1
]}

Noh, Sung Hoon ^{[1
,18
]}

Cheong, Jae-Ho ^{[1
,2
,18
,19
]}

机构：

[1] Yonsei Univ Hlth Syst, Dept Surg, Seoul, South Korea

[2] Yonsei Biomed Res Inst, Seoul, South Korea

[3] Yonsei Univ, Dept Pathol, Coll Med, Seoul, South Korea

[4] Hanyang Univ, Coll Med, Dept Pathol, Seoul, South Korea

[5] Yonsei Univ, Coll Med, Biostat Collaborat Unit, Seoul, South Korea

[6] Dept Surg, Seoul, South Korea

[7] Canc Res Inst, Seoul, South Korea

[8] Seoul Natl Univ, Dept Pathol, Coll Med, Seoul, South Korea

[9] Natl Canc Ctr, Ctr Gastr Canc, Goyang Si, Gyeonggi Do, South Korea

[10] Chonnam Natl Univ, Dept Surg, Hwasun Hosp, Jeonnam, South Korea

[11] Seoul Natl Univ, Bundang Hosp, Dept Surg, Coll Med, Seongnam, Gyeonggi Do, South Korea

[12] Seoul Natl Univ, Coll Med, Dept Pathol, Bundang Hosp, Seongnam, Gyeonggi Do, South Korea

[13] Yeungnam Univ, Coll Med, Dept Internal Med, Daegu, South Korea

[14] Yeungnam Univ, Coll Med, Dept Pathol, Daegu, South Korea

[15] Gangnam Severance Hosp, Dept Surg, Seoul, South Korea

[16] Gangnam Severance Hosp, Dept Pathol, Seoul, South Korea

[17] Chung Ang Univ, Coll Med, Dept Surg, Chung Ang Univ Hosp, Seoul, South Korea

[18] Yonsei Univ, Coll Med, Brain Korea 21 Plus Project Med Sci, Seoul, South Korea

[19] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea

来源：

ANNALS OF SURGERY | 2019年 / 270卷 / 02期

关键词：

biomarker; chemotherapy; gastric cancer; microsatellite instability; programmed cell death ligand 1; III COLON-CANCER; MISMATCH REPAIR; ADJUVANT CAPECITABINE; ANTI-PD-L1; ANTIBODY; PROTEIN EXPRESSION; COLORECTAL-CANCER; PROGNOSTIC-FACTOR; PD-L1; EXPRESSION; BRAF MUTATION; OPEN-LABEL;

D O I：

10.1097/SLA.0000000000002803

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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.

引用

页码：309 / 316

页数：8