Glutathione peroxidase 2 expression in human tumors: a tissue microarray study on 18,555 tumors

Our plain-English summary of Glutathione peroxidase 2 expression in human tumors: a tissue microarray study on 18,555 tumors, by V. Chirico, N. Jahn, S. Büyücek, et al (Frontiers in Oncology, 2026).

The study

• Authors: V. Chirico, N. Jahn, S. Büyücek, N. Schraps, M. Lennartz, K. Möller, E. Bady, L. Hornsteiner, H. Plage, C. Hube-Magg, M. Kluth, F. Jacobsen, F. Viehweger, D. Dum, A. Hinsch, C. Fraune, C. Bernreuther, P. Lebok, G. Sauter, T.S. Clauditz, T. Krech, A.H. Marx, R. Simon, E. Burandt, N. Gorbokon, S. Minner, S. Steurer
• Journal: Frontiers in Oncology
• Published: 2026;16:1809848
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Glutathione peroxidase 2 (GPX2) has a pivotal role in removing reactive oxygen species (ROS) from cells. Although the number of studies analyzing GPX2 in cancer is still limited, data suggesting a role of altered GPX2 expression in various cancer types are accumulatin.

Methods: To better comprehend the role of GPX2 expression in cancer, GPX2 was analyzed by immunohistochemistry on tissue microarrays containing 18,555 samples from 148 different tumor types.

Results: A total of 95 of 148 tumor categories showed GPX2 expression in at least one case, and 61 tumor categories contained at least one strongly positive case. GPX2 positivity was most seen in colorectal adenocarcinomas (97.9%) and adenomas (100%), non-invasive urothelial carcinomas (88.9-100%), pancreatico-biliary cancers (83.4-94.7%), Brenner tumors of the ovary (89.7%), gastro-esophageal adenocarcinomas (83.1-87.3%), and seminomas (85.6%). Clinically important cancer types with infrequent and often weak GPX2 staining included sarcomas, lymphomas, high-grade serous ovarian carcinomas, prostatic adenocarcinomas, melanomas, mesotheliomas, and renal cell carcinomas. Reduced GPX2 staining was linked to microsatellite instability (MSI, p<0.0001), advanced pT stage (p=0.0044), nodal metastasis (p=0.0093), V1 (p=0.0020) and L1 (p=0.0057) in colorectal adenocarcinoma, invasive growth (p<0.0001), high grade (p=0.0013), nodal metastasis (p=0.0005), V1 (p=0.0004) and L1 (p=0.0001) in urothelial carcinoma, high grade in pancreatic ductal adenocarcinoma (p=0.0233), and MSI in gastric adenocarcinoma (p=0.0325).

Conclusion: It is concluded, that GPX2 expression is common in cancer and preferably occurs in tumor entities derived from normal cell types with high GPX2 expression. In these tumors, reduced GPX2 expression is often linked to features of aggressive disease.

Copyright © 2026 Chirico, Jahn, Büyücek, Schraps, Lennartz, Möller, Bady, Hornsteiner, Plage, Hube-Magg, Kluth, Jacobsen, Viehweger, Dum, Hinsch, Fraune, Bernreuther, Lebok, Sauter, Clauditz, Krech, Marx, Simon, Burandt, Gorbokon, Minner and Steurer.

In plain English

This study did not look at asbestos or any other exposure. The authors stained 18,555 archived primary tumors of 148 types for glutathione peroxidase 2 (GPX2), a protein that helps remove reactive oxygen species from cells; 15,654 could be evaluated. GPX2 was found in 5,919 (37.8%), with particularly frequent staining in colorectal adenocarcinomas (97.9%) and adenomas (100%). All 31 evaluable epithelioid and all 21 evaluable biphasic mesotheliomas were negative. In colorectal adenocarcinoma, the authors reported reduced GPX2 with microsatellite instability, advanced stage, lymph node spread and blood vessel invasion. Their text also reports a link with lymphatic invasion, which their table does not support (p=0.3041). In urothelial carcinoma, reduced GPX2 was linked to invasive growth and high grade. Reported links with lymph node spread and blood vessel and lymphatic invasion conflict with the table, which shows more GPX2-positive tumors with these features. Reduced GPX2 was linked to high grade in pancreatic ductal adenocarcinoma. The authors concluded that GPX2 is common in cancer, mainly in tumors from GPX2-rich cell types, where reduced GPX2 is often linked to aggressive features. They noted the loss might reflect tumor dedifferentiation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of archived tumor tissue: immunohistochemistry (protein staining) on tissue microarrays
• Who was studied: 18,555 archived primary tumors of 148 tumor types and subtypes from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany; 15,654 were evaluable. Collection dates are not given.
• Exposure: Not studied. The article does not examine asbestos or any other exposure. What it measured was GPX2 protein staining in tumors.
• Main results:
  • 15,654 (84.4%) of the 18,555 tumor samples could be interpreted.
  • GPX2 staining was detected in 5,919 (37.8%) of the 15,654 analyzable tumors.
  • The authors listed several tumor types as the ones most often GPX2 positive. These included colorectal adenocarcinomas (97.9%), colorectal adenomas (100%) and non-invasive urothelial carcinomas (88.9-100%).
  • No malignant mesothelioma was GPX2 positive (0.0%).
  • Of the epithelioid mesotheliomas, 40 were on the microarray and 31 were analyzable, and 100.0% were negative. Of the biphasic mesotheliomas, 29 were on the microarray and 21 were analyzable, and 100.0% were negative.
  • In colorectal adenocarcinoma, the text reports reduced GPX2 staining linked to advanced pT stage (p=0.0044), nodal metastasis (p=0.0093) and blood vessel invasion V1 (p=0.002). It also reports a link with microsatellite instability (p less than 0.0001).
  • For lymphatic invasion (L1) in all colorectal adenocarcinomas, the text gives p=0.0057, but Table 2 gives p=0.3041, which is not significant. In the mismatch-repair-proficient subgroup, Table 2 gives p=0.0038, with strong staining in 93.4% of L0 versus 86.2% of L1 tumors.
  • In urothelial carcinoma, reduced GPX2 staining was linked to invasive disease (p less than 0.0001). In muscle-invasive tumors it was linked to high grade (p=0.0013): strong staining was seen in 64% of G2 versus 31.2% of G3 tumors.
  • For muscle-invasive urothelial carcinoma, the text links reduced GPX2 with nodal metastasis (p=0.0005), V1 (p=0.0004) and L1 (p=0.0001). Table 2 shows the opposite direction. Negative tumors were 25.9% with V1 versus 49.8% with V0, and 31.1% with L1 versus 53.6% with L0. Strong staining was 45.9% with V1 versus 28% with V0.
  • Reduced GPX2 staining was linked to high grade in pancreatic ductal adenocarcinoma (p=0.0233).
  • GPX2 level was unrelated to features of cancer aggressiveness in endometrioid ovarian carcinoma, endometrial carcinoma, hepatocellular carcinoma, and follicular and papillary thyroid cancer.
• The authors' conclusion: The authors concluded that GPX2 expression is common in cancer and occurs mainly in tumors derived from normal cell types with high GPX2 expression. In these tumors, they said, reduced GPX2 expression is often linked to features of aggressive disease.
• Limitations the authors state:
  • The authors could not exclude that loss of GPX2 is caused by random changes during tumor-cell dedifferentiation, rather than playing a role in aggressive behavior.

Topics

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Reactive Oxygen Species (ROS), Immunohistochemistry, Adenocarcinoma, Carcinoma, Sarcoma, Mesothelioma, Microsatellite Instability (MSI-H).

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