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Tumor-Associated CD68+, CD163+, and MARCO+ Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma

Jeremiasen, Martin LU ; Borg, David LU ; Hedner, Charlotta LU ; Svensson, Maria LU ; Nodin, Björn LU ; Leandersson, Karin LU orcid ; Johansson, Jan LU and Jirström, Karin LU orcid (2020) In Frontiers in Oncology 10.
Abstract

Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive,... (More)

Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan–Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68+ and CD163+, but not MARCO+, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68+ TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163+ TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68+ macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02–2.55, and p = 0.041). Conclusion: Infiltration of CD68+ and CD163+, but not MARCO+, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
esophageal cancer, gastric cancer, macrophages, prognosis, treatment naïve
in
Frontiers in Oncology
volume
10
article number
534761
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33194593
  • scopus:85095566537
ISSN
2234-943X
DOI
10.3389/fonc.2020.534761
language
English
LU publication?
yes
id
e793a25a-bf7f-459e-bda6-26cac2b66c5e
date added to LUP
2021-01-13 23:42:41
date last changed
2024-04-03 21:45:12
@article{e793a25a-bf7f-459e-bda6-26cac2b66c5e,
  abstract     = {{<p>Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68<sup>+</sup>, CD163<sup>+</sup>, and MARCO<sup>+</sup> macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan–Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68<sup>+</sup> and CD163<sup>+</sup>, but not MARCO<sup>+</sup>, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68<sup>+</sup> TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163<sup>+</sup> TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68<sup>+</sup> macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02–2.55, and p = 0.041). Conclusion: Infiltration of CD68<sup>+</sup> and CD163<sup>+</sup>, but not MARCO<sup>+</sup>, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.</p>}},
  author       = {{Jeremiasen, Martin and Borg, David and Hedner, Charlotta and Svensson, Maria and Nodin, Björn and Leandersson, Karin and Johansson, Jan and Jirström, Karin}},
  issn         = {{2234-943X}},
  keywords     = {{esophageal cancer; gastric cancer; macrophages; prognosis; treatment naïve}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Oncology}},
  title        = {{Tumor-Associated CD68<sup>+</sup>, CD163<sup>+</sup>, and MARCO<sup>+</sup> Macrophages as Prognostic Biomarkers in Patients With Treatment-Naïve Gastroesophageal Adenocarcinoma}},
  url          = {{http://dx.doi.org/10.3389/fonc.2020.534761}},
  doi          = {{10.3389/fonc.2020.534761}},
  volume       = {{10}},
  year         = {{2020}},
}