Introduction Campylobacter concisus has recently been implicated in the pathogenesis of a number of gastrointestinal diseases. In vitro studies have shown that these bacteria can induce apoptosis in epithelial cells and their presence may induce altered expression of genes. Our group has reported that C. concisus was isolated from the Barrett’s mucosa in 57% of affected patients but was not identified in normal oesophagogastric mucosa. From this series of cases of known C concisus status we have examined the expression of a range of molecular markers associated with cancer development to correlate their pattern of expression with the presence of C. concisus. The aim of this study was to investigate whether C concisus may contribute to malignant progression of BO, the major risk factor for the development of oesophageal adenocarcinoma (OA).
Methods Tissue microarrays (TMA) were prepared from samples of BO (n = 92), severe dysplasia (n = 39) and OA (n = 64). Paired biopsies were collected from a separate patient cohort with BO and formalin-fixed or used for Taqman PCR to determine C. concisus colonisation status (14 colonised and 13 uncolonised). The TMAs and BO slides were immunohistochemically stained for Ki-67, phospho-p53 Ser 15 and COX-2. Slides were semi-quantitatively scored 0–3 according to staining intensity of COX-2 and Ki-67. For phospho-p53, intensity of staining and percentage of glands stained were scored to derive a multiplicative phospho-p53 score. All slides were scored by a single blinded observer. Median scores were used in statistical testing, with p < 0.05 considered as significant. Results are presented in mean ± SEM unless stated otherwise.
Results Patient characteristics were similar between TMA samples [median age 70(24–91), 69.7% males] and the C. concisus BO cohort [median age 62(41–84), 66.7% males]. TMA staining patterns of Ki-67, phospho-p53 and COX-2 changed significantly from BO to OA, which is consistent with widely published results in the literature. This validates our method of scoring and staining. C. concisus colonised and uncolonised BO did not significantly differ in expression of Ki-67 (1.79 ± 0.21 vs. 1.92 ± 0.24) or phospho-p53 (0.15 ± 0.10 vs. 0.50 ± 0.25). However, C. concisus colonised BO (n = 8) was associated with lower expression of COX-2 compared to uncolonised BO (n = 13), after the exclusion of samples from patients taking NSAIDs from the analysis (1.13 ± 0.13 vs. 1.69 ± 0.17, p = 0.0371).
Conclusion C. concisus status in BO was not associated with altered expression of phospho-p53 or Ki-67. However, the presence of C. concisus was associated with reduced COX-2 expression raising the possibility that the bacteria may induce a phenotype protective against the development of OA.
Disclosure of Interest None Declared
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