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

• Published in: Virchows Archiv : an international journal of pathology 2022-09, Vol.481 (3), p.467-476
• Main Authors: Helminen, Olli, Melkko, Jukka, Saarnio, Juha, Sihvo, Eero, Kuopio, Teijo, Ohtonen, Pasi, Kauppila, Joonas H., Karttunen, Tuomo J., Huhta, Heikki
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - pathology; Barrett Esophagus - pathology; Barrett's esophagus; Cancer; Case studies; Case-Control Studies; Dysplasia; Endoscopy; Esophageal cancer; Esophageal Neoplasms - pathology; Esophagus; Humans; Ki-67 Antigen - metabolism; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Metaplasia; Original; Original Article; p53 Protein; Pathology; Patients; Retrospective Studies; TLR5 protein; Toll-Like Receptor 5 - metabolism; Toll-like receptors; Tumor Suppressor Protein p53
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-022-03340-5

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.