University of Oulu

Helminen, O., Melkko, J., Saarnio, J. et al. Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett’s esophagus: a matched case–control study. Virchows Arch 481, 467–476 (2022).

Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett’s esophagus : a matched case–control study

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Author: Helminen, Olli1,2; Melkko, Jukka1; Saarnio, Juha1;
Organizations: 1Surgery Research Unit, Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, N90014 University of Oulu , PO-box 5000, Oulu, Finland
2Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
3Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland
4Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland
5Division of Operative Care, Oulu University Hospital, Oulu, Finland
6Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2023-06-29


Barrett’s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett’s metaplasia and low-grade dysplasia. This was a retrospective matched case–control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett’s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett’s metaplasia (n = 21) or low-grade dysplasia (n  = 24), and 92 patients with non-progressive Barrett’s metaplasia (n  = 52) or low-grade dysplasia (n  = 40). In Barrett’s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd’s ratio 6.7, 95% CI 1.8–24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case–control study, p53 expression associated with a high risk of malignant progression in Barrett’s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.

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Series: Virchows Archiv. European journal of pathology
ISSN: 0945-6317
ISSN-E: 1432-2307
ISSN-L: 0945-6317
Volume: 481
Issue: 3
Pages: 467 - 476
DOI: 10.1007/s00428-022-03340-5
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3111 Biomedicine
Funding: Open Access funding provided by University of Oulu including Oulu University Hospital. This study was funded by Instrumentarium Science Foundation (OH), Mary and Georg C. Ehrnrooth Foundation (OH, JHK), and Finnish State Research Funding (OH, HH), Finnish Cultural Foundation (HH), Vieno, Alli Suorsa’s Healthcare Foundation (HH), The Finnish Cancer Foundation (JHK), Sigrid Juselius Foundation (JHK), and Päivikki and Sakari Sohlberg Foundation (JHK).
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