Mesothelin Expression Is a Predictive Factor for Peritoneal Recurrence in Curatively Resected Stage III Gastric Cancer

Su Jin Shin, Sejung Park, Min Hwan Kim, Chung Mo Nam, Hyunki Kim, Yoon Young Choi, Min Kyu Jung, Hye Jin Choi, SunYoung Rha, Hyuncheol Chung

Research output: Contribution to journalArticle

Abstract

Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. Subjects, Materials, and Methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. Results: High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p =.021) and peritoneal recurrence (p =.018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p =.001), OS (p =.001), and peritoneal recurrence (p =.002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p =.013) and diffuse/mixed type gastric cancer (p =.010). Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. Implications for Practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

Original languageEnglish
JournalOncologist
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Stomach Neoplasms
Recurrence
Survival
Neoplasms
mesothelin
Clinical Trials
Survival Analysis
Immunotherapy
Anti-Idiotypic Antibodies
Multivariate Analysis
Staining and Labeling
Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shin, Su Jin ; Park, Sejung ; Kim, Min Hwan ; Nam, Chung Mo ; Kim, Hyunki ; Choi, Yoon Young ; Jung, Min Kyu ; Choi, Hye Jin ; Rha, SunYoung ; Chung, Hyuncheol. / Mesothelin Expression Is a Predictive Factor for Peritoneal Recurrence in Curatively Resected Stage III Gastric Cancer. In: Oncologist. 2019.
@article{cf864520d5424397987213013b94ec3e,
title = "Mesothelin Expression Is a Predictive Factor for Peritoneal Recurrence in Curatively Resected Stage III Gastric Cancer",
abstract = "Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. Subjects, Materials, and Methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. Results: High mesothelin expression was observed in 49.7{\%} of patients and significantly associated with high pathologic T (p =.021) and peritoneal recurrence (p =.018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p =.001), OS (p =.001), and peritoneal recurrence (p =.002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p =.013) and diffuse/mixed type gastric cancer (p =.010). Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. Implications for Practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.",
author = "Shin, {Su Jin} and Sejung Park and Kim, {Min Hwan} and Nam, {Chung Mo} and Hyunki Kim and Choi, {Yoon Young} and Jung, {Min Kyu} and Choi, {Hye Jin} and SunYoung Rha and Hyuncheol Chung",
year = "2019",
month = "1",
day = "1",
doi = "10.1634/theoncologist.2018-0896",
language = "English",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",

}

Mesothelin Expression Is a Predictive Factor for Peritoneal Recurrence in Curatively Resected Stage III Gastric Cancer. / Shin, Su Jin; Park, Sejung; Kim, Min Hwan; Nam, Chung Mo; Kim, Hyunki; Choi, Yoon Young; Jung, Min Kyu; Choi, Hye Jin; Rha, SunYoung; Chung, Hyuncheol.

In: Oncologist, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mesothelin Expression Is a Predictive Factor for Peritoneal Recurrence in Curatively Resected Stage III Gastric Cancer

AU - Shin, Su Jin

AU - Park, Sejung

AU - Kim, Min Hwan

AU - Nam, Chung Mo

AU - Kim, Hyunki

AU - Choi, Yoon Young

AU - Jung, Min Kyu

AU - Choi, Hye Jin

AU - Rha, SunYoung

AU - Chung, Hyuncheol

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. Subjects, Materials, and Methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. Results: High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p =.021) and peritoneal recurrence (p =.018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p =.001), OS (p =.001), and peritoneal recurrence (p =.002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p =.013) and diffuse/mixed type gastric cancer (p =.010). Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. Implications for Practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

AB - Background: Mesothelin is overexpressed in many solid tumors, and recent studies have shown that mesothelin expression is associated with poor outcomes in several malignant tumors and may play a role in cancer progression. Clinical trials of mesothelin-targeted immunotherapies are currently under way, but the correlation between mesothelin expression and gastric cancer prognosis is still unclear. Subjects, Materials, and Methods: Mesothelin expression in tumor cells was evaluated immunohistochemically in 958 patients with advanced gastric cancer and interpreted according to the intensity and extent of staining. Samples were scored from 0 to 2, with high expression defined as a score of 2. Clinicopathological factors, overall survival (OS), recurrence-free survival (RFS), and sites of initial recurrence, including peritoneal recurrence, were evaluated. Staging was performed according to the American Joint Committee on Cancer 7th edition. Results: High mesothelin expression was observed in 49.7% of patients and significantly associated with high pathologic T (p =.021) and peritoneal recurrence (p =.018). Multivariate survival analysis showed that high mesothelin expression was independently associated with poor RFS (p =.001), OS (p =.001), and peritoneal recurrence (p =.002) in addition to stage, lymphovascular invasion, and Lauren classification. In a subgroup analysis of peritoneal recurrence, high mesothelin expression was also an independent prognostic factor in stage III (p =.013) and diffuse/mixed type gastric cancer (p =.010). Conclusion: High mesothelin expression is correlated with poor outcomes. In addition, mesothelin expression, Lauren classification, and stage are meaningful predictive factors for peritoneal recurrence. Moreover, mesothelin was a significant predictor of a high risk of peritoneal recurrence in patients with stage III gastric cancer. Implications for Practice: This study demonstrates that high mesothelin expression correlates with poor outcomes and is a significant predictor of peritoneal recurrence in patients with stage III gastric cancer. This study provides instrumental evidence for designing anti-mesothelin antibody-drug conjugate clinical trials in patients with diffuse-type gastric cancer to reduce their high risk of peritoneal carcinomatosis.

UR - http://www.scopus.com/inward/record.url?scp=85064764424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064764424&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.2018-0896

DO - 10.1634/theoncologist.2018-0896

M3 - Article

JO - Oncologist

JF - Oncologist

SN - 1083-7159

ER -