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, Soon Won Hong, Jong Won Kim, Woo Jin Hyung, Sung Hoon Noh, Jae Ho Cheong

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)309-316
Number of pages8
JournalAnnals of surgery
Volume270
Issue number2
DOIs
Publication statusPublished - 2019 Aug 1

Fingerprint

Microsatellite Instability
Stomach Neoplasms
Cell Death
Ligands
Disease-Free Survival
Adjuvant Chemotherapy
Neoplasms
oxaliplatin
Stromal Cells
Microsatellite Repeats
Immunohistochemistry
Drug Therapy
Gastrectomy
Randomized Controlled Trials
Biomarkers
Survival

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

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, Soon Won ; Kim, Jong Won ; Hyung, Woo Jin ; Noh, Sung Hoon ; Cheong, Jae Ho. / Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer : Post Hoc Analysis of the CLASSIC Randomized Controlled study. In: Annals of surgery. 2019 ; Vol. 270, No. 2. pp. 309-316.
@article{8cfbac8602854bb4ac40224d7be210df,
title = "Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study",
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.",
author = "Choi, {Yoon Young} and Hyunki Kim and Shin, {Su Jin} and Kim, {Ha Yan} and Jinae Lee and Yang, {Han Kwang} and Kim, {Woo Ho} and Kim, {Young Woo} and Kook, {Myeong Cherl} and Park, {Young Kyu} and Kim, {Hyung Ho} and Lee, {Hye Seung} and Lee, {Kyung Hee} and Gu, {Mi Jin} and Choi, {Seung Ho} and Hong, {Soon Won} and Kim, {Jong Won} and Hyung, {Woo Jin} and Noh, {Sung Hoon} and Cheong, {Jae Ho}",
year = "2019",
month = "8",
day = "1",
doi = "10.1097/SLA.0000000000002803",
language = "English",
volume = "270",
pages = "309--316",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

Choi, YY, Kim, H, Shin, SJ, Kim, HY, Lee, J, Yang, HK, Kim, WH, Kim, YW, Kook, MC, Park, YK, Kim, HH, Lee, HS, Lee, KH, Gu, MJ, Choi, SH, Hong, SW, Kim, JW, Hyung, WJ, Noh, SH & Cheong, JH 2019, 'Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer: Post Hoc Analysis of the CLASSIC Randomized Controlled study', Annals of surgery, vol. 270, no. 2, pp. 309-316. https://doi.org/10.1097/SLA.0000000000002803

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, Soon Won; Kim, Jong Won; Hyung, Woo Jin; Noh, Sung Hoon; Cheong, Jae Ho.

In: Annals of surgery, Vol. 270, No. 2, 01.08.2019, p. 309-316.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer

T2 - Post Hoc Analysis of the CLASSIC Randomized Controlled study

AU - Choi, Yoon Young

AU - Kim, Hyunki

AU - Shin, Su Jin

AU - Kim, Ha Yan

AU - Lee, Jinae

AU - Yang, Han Kwang

AU - Kim, Woo Ho

AU - Kim, Young Woo

AU - Kook, Myeong Cherl

AU - Park, Young Kyu

AU - Kim, Hyung Ho

AU - Lee, Hye Seung

AU - Lee, Kyung Hee

AU - Gu, Mi Jin

AU - Choi, Seung Ho

AU - Hong, Soon Won

AU - Kim, Jong Won

AU - Hyung, Woo Jin

AU - Noh, Sung Hoon

AU - Cheong, Jae Ho

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85069851897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069851897&partnerID=8YFLogxK

U2 - 10.1097/SLA.0000000000002803

DO - 10.1097/SLA.0000000000002803

M3 - Article

C2 - 29727332

AN - SCOPUS:85069851897

VL - 270

SP - 309

EP - 316

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 2

ER -