Immunohistochemical assessment of Survivin and Bcl3 expression as potential biomarkers for NF‐κB activation in the Barrett metaplasia–dysplasia–adenocarcinoma sequence

Abstract

Non-dysplastic Barrett's oesophagus (NDBE) occurs as a consequence of an inflammatory response triggered through prolonged gastro-oesophageal reflux and it may precede the development of oesophageal adenocarcinoma. NF-κB activation as a result of the inflammatory response has been shown in NDBE, but the possible mechanism involved in the process is unknown. The aim of this study was to assess, using immunohistochemistry, Survivin and Bcl3 expression as potential biomarkers for NF-κB activation along the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. Survivin is an NF-κB-inducible anti-apoptotic protein, and Bcl3 is a negative regulator of NF-κB. There was progressive upregulation of Survivin expression along the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. Bcl3 expression was upregulated in non-dysplastic Barrett's oesophagus, low-grade, high-grade dysplasia and oesophageal adenocarcinoma when compared to squamous group. The study shows the differential expression of Bcl3 between the squamous and Barrett's stage, suggesting that Bcl3 could be a surrogate marker for early event involving constitutive NF-κB activation. In addition, the study suggests that NF-κB activation may infer resistance to apoptosis through the expression of anti-apoptotic genes such as Survivin, which showed progressive increase in expression throughout the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. This ability to avoid apoptosis may underlie the persistence and malignant predisposition of Barrett's metaplasia.

Topical Application of Temperature-Sensitive Gel Containing Caerin 1.1 and 1.9 Peptides on TC-1 Tumour-Bearing Mice Induced High-Level Immune Response in the Tumour Microenvironment

“…The FC and p -values of the top 40 significantly regulated genes were summarised in Figure S6A . The upregulation of four genes relevant to the activation of NF-κB signalling was detected, including Bcl3 ( 43 ), Tradd ( 44 ), Mtdh ( 45 ) and Ncoa6 ( 46 ), indicating more pro-inflammatory migDCs in the caerin group. The overall gene expression of the four DCs was compared, which showed that Ly6a , Tmed7 , H2-Oa , Bag1 and Cebpb were significantly elevated by the caerin gel ( Figure S6B ).…”

Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

“…BCL3 is a proto-oncogene candidate gene with the function of transcriptional co-activation that activates through its association with NF-κB homodimers. The expression of BCL3 gene can be induced by NF-κB, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-κB [ 46 ]. The mutations in BCL3 have been associated with HDL-C level, fasting insulin level and Alzheimer's disease (AD) [ 47 ].…”

Survivin in lung cancer: a potential target for therapy and prevention—a narrative review

“…Kawasaki et al showed increased survivin immunoreactivity along the adenoma-carcinoma sequence providing evidence for the role of survivin in tumorigenesis ( 32 ). Puccio et al studied the expression of survivin in non-dysplastic Barrett’s esophagus, concluding that survivin levels progressively increase in the transition from metaplasia to dysplasia to adenocarcinoma ( 35 ). Similarly, Nakanishi et al studied levels of survivin in various premalignant lesions of lung cancer low-grade atypical adenomatous hyperplasia (AAH), high-grade AAH, and adenocarcinoma ( 36 ).…”