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Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases

Malmros, Karina LU ; Lindholm, Andreas ; Vidarsdottir, Halla LU ; Jirström, Karin LU orcid ; Nodin, Björn LU ; Botling, Johan ; Mattsson, Johanna S.M. ; Micke, Patrick ; Planck, Maria LU and Jönsson, Mats LU , et al. (2024) In Virchows Archiv 485. p.347-357
Abstract

Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from... (More)

Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from colorectal cancer, pancreatic cancer, and other GI adenocarcinomas, respectively), CDX2 (99/40/100%), and CDH17 (99/0/100%). In comparison, SATB2 and CK20 showed higher specificity, with expression in 5% and 10% of mucinous primary lung adenocarcinomas and both in 0% of TTF-1-negative non-mucinous primary lung adenocarcinomas (25–50% and 5–16%, respectively, for GPA33/CDX2/CDH17). MUC2 was negative in all primary lung cancers, but positive only in less than half of pulmonary metastases from mucinous adenocarcinomas from other organs. Combining six GI markers did not perfectly separate primary lung cancers from pulmonary metastases including subgroups such as mucinous adenocarcinomas or CK7-positive GI tract metastases. This comprehensive comparison suggests that CDH17, GPA33, and SATB2 may be used as equivalent alternatives to CDX2 and CK20. However, no single or combination of markers can categorically distinguish primary lung cancers from metastatic GI tract cancer.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A33, Cadherin 17, CDX2, CK20, Immunohistochemistry, MUC2, SATB2
in
Virchows Archiv
volume
485
pages
347 - 357
publisher
Springer
external identifiers
  • scopus:85163027637
  • pmid:37349623
ISSN
0945-6317
DOI
10.1007/s00428-023-03583-w
project
Histopathological and molecular diagnostics of lung cancer
language
English
LU publication?
yes
additional info
Funding Information: Open access funding provided by Lund University. The study was supported by Swedish governmental funding of clinical research (ALF), the Franke and Margareta Bergqvist Foundation, and the Swedish Cancer Society. The funding sources had no role in the design or conduct of the study. Publisher Copyright: © 2023, The Author(s).
id
f479c5b9-2032-40a4-8d52-0d37dbad5bf8
date added to LUP
2023-07-06 14:43:19
date last changed
2024-11-30 22:50:57
@article{f479c5b9-2032-40a4-8d52-0d37dbad5bf8,
  abstract     = {{<p>Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from colorectal cancer, pancreatic cancer, and other GI adenocarcinomas, respectively), CDX2 (99/40/100%), and CDH17 (99/0/100%). In comparison, SATB2 and CK20 showed higher specificity, with expression in 5% and 10% of mucinous primary lung adenocarcinomas and both in 0% of TTF-1-negative non-mucinous primary lung adenocarcinomas (25–50% and 5–16%, respectively, for GPA33/CDX2/CDH17). MUC2 was negative in all primary lung cancers, but positive only in less than half of pulmonary metastases from mucinous adenocarcinomas from other organs. Combining six GI markers did not perfectly separate primary lung cancers from pulmonary metastases including subgroups such as mucinous adenocarcinomas or CK7-positive GI tract metastases. This comprehensive comparison suggests that CDH17, GPA33, and SATB2 may be used as equivalent alternatives to CDX2 and CK20. However, no single or combination of markers can categorically distinguish primary lung cancers from metastatic GI tract cancer.</p>}},
  author       = {{Malmros, Karina and Lindholm, Andreas and Vidarsdottir, Halla and Jirström, Karin and Nodin, Björn and Botling, Johan and Mattsson, Johanna S.M. and Micke, Patrick and Planck, Maria and Jönsson, Mats and Staaf, Johan and Brunnström, Hans}},
  issn         = {{0945-6317}},
  keywords     = {{A33; Cadherin 17; CDX2; CK20; Immunohistochemistry; MUC2; SATB2}},
  language     = {{eng}},
  pages        = {{347--357}},
  publisher    = {{Springer}},
  series       = {{Virchows Archiv}},
  title        = {{Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases}},
  url          = {{http://dx.doi.org/10.1007/s00428-023-03583-w}},
  doi          = {{10.1007/s00428-023-03583-w}},
  volume       = {{485}},
  year         = {{2024}},
}