Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus

Kastelein, Florine; Biermann, Katharina; Steyerberg, Ewout W.; Verheij, Joanne; Kalisvaart, Marit; Looijenga, Leendert H. J.; Stoop, Hans; Walter, Laurens; Kuipers, Ernst J.; Spaander, Manon; Bruno, Marco J.

doi:10.1136/gutjnl-2012-303594

Cited by 219 publications

(193 citation statements)

References 38 publications

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“…Recent promising work in a case-control study suggested that aberrant p53 expression defi ned as absent or increased expression by immunohistochemistry was associated with an increased risk of neoplastic progression ( 134 ). However, it appears that no single biomarker is adequate as a risk stratifi cation tool.…”

Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

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Recent population studies suggest that gastroesophageal refl ux disease (GERD) is increasing in prevalence, both in the United States and worldwide ( 1,2 ). Th e diagnosis of GERD is associated with a 10-15% risk of Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM). Risk factors associated with the development of BE include long-standing GERD, male gender, central obesity ( 3 ), and age over 50 years ( 4,5 ). Th e goal of a screening and surveillance program for BE is to identify individuals at risk for progression to esophageal adenocarcinoma (EAC), a malignancy that has been increasing in incidence since the 1970s ( 6,7 ).Th e purpose of this guideline is to review the defi nition and epidemiology of BE, available screening modalities for BE detection, rationale and methods for surveillance, and available treatment modalities including medical, endoscopic, and surgical techniques. In order to evaluate the level of evidence and strength of recommendations, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system ( 8 ). Th e level of evidence ranged from "high" (implying that further research was unlikely to change the authors' confi dence in the estimate of the eff ect) to "moderate" (further research would be likely to have an impact on the confi dence in the estimate of eff ect) to "low" (further research would be expected to have an important impact on the confi dence in the estimate of the eff ect and would be likely to change the estimate) or "very low" (any estimate of eff ect is very uncertain). Th e strength of a recommendation was graded as "strong" when the desirable eff ects of an intervention clearly outweighed the undesirable eff ects and as "conditional" when there was uncertainty about the tradeoff s. We used meta-analyses or systematic reviews when available, followed by clinical trials and cohort and case-control studies. In order to determine the level Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with refl ux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-defi nition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is ...

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Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

View full text Add to dashboard Cite

show abstract

“…It is, however, the overexpression of p53 in LGD that is associated with an increased risk of progression to HGD/EAC [24][25][26] . The concomitant diagnosis of aberrant p53 increased the positive predictive value of neoplastic progression from 15% to 33% [27] . Further the presence of 17p loss of heterozygosity (LOH), which is thought to represent inactivation of p53 has been demonstrated to be a strong predictor of progression in BE [28] .…”

Section: Esophageal Adenocarcinomamentioning

confidence: 96%

Low grade dysplasia in Barrett’s esophagus: Should we worry?

Jagadesham

2014

WJGP

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The optimal management for low-grade dysplasia (LGD) in Barrett's esophagus is unclear. In this article the importance of LGD is discussed, including the significant risk of progression to esophageal adenocarcinoma. Endoscopic surveillance is a management option but is plagued by sampling error and issues of suboptimal endoscopy. Furthermore endoscopic surveillance has not been demonstrated to be cost-effective or to reduce cancer mortality. The emergence of endoluminal therapy over the past decade has resulted in a paradigm shift in the management of LGD. Ablative therapy, including radiofrequency ablation, has demonstrated promising results in the management of LGD with regards to safety, cost-effectiveness, durability and reduction in cancer risk. It is, however, vital that a shareddecision making process occurs between the physician and the patient as to the preferred management of LGD. As such the management of LGD should be "individualised." Core tip: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is an important entity and poses a significant risk of progression to esophageal adenocarcinoma. With the emergence of endoluminal therapy over the past decade there has been a paradigm shift in the management of LGD. Ablative therapy, such as radiofrequency ablation, has demonstrated promising results in the management of LGD with regards to safety, costeffectiveness, durability and reduction in cancer risk. It is, however, critical that management should be through a shared-decision making process and "individualised". It is our belief that physicians should "worry " about LGD in BE.Jagadesham VP, Kelty CJ. Low grade dysplasia in Barrett's esophagus: Should we worry? World J Gastrointest Pathophysiol 2014; 5(2): 91-99 Available from:

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“…Extensive evidence shows that p53 overexpression is seen in both cancerous and high grade dysplasia and is, thus, predictive of progression [16]. This could be an excellent predictive tool when its overexpression is detected by immunohistochemistry [17]. Due to the complexity of the control of the cell cycle and the amount of genetic alterations that can occur, it is likely that mutations will vary between patients and there may not be a single trigger that will be able to explain, nor predict, progression, but rather an accumulation of changes that will ultimately push the cell towards carcinoma.…”

Section: Dysplasiamentioning

confidence: 99%

Detection of dysplasia in Barrett’s oesophagus: Are there impending optical and spectroscopic solutions?

Upchurch¹,

Old²,

Gr³

et al. 2016

Gastroenterol Hepatol Endosc

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The incidence of Barrett's oesophagus and oesophageal adenocarcinoma is increasing in Western countries. The outcome for patients with oesophageal cancer is extremely poor with only 15.1% of patients surviving for 5 years. The dismal outcome is largely due to late diagnosis which eliminates many patients from effective treatment.Oesophageal adenocarcinoma is often preceded by the development of dysplasia in a segment of Barrett's oesophagus. With the current surveillance strategies, it is extremely difficult to not only visualise areas of dysplasia, but also to accurately identify their morphological and architectural changes during histopathological diagnosis. Consensus statements recommend mucosal resection for dysplastic change in the oesophagus, thereby, preventing the development of adenocarcinoma. This strategy requires improved diagnostic tools that can reliably distinguish patients with dysplasia.Years of research have looked at a variety of different modalities that may aid with the current dilemma of difficulties in diagnosing dysplasia. This review looks at the modalities under development and analyses their advantages and the part they may well play in the future. It also looks at the future avenues that could be explored to aid in the understanding of the disease and to improve the outcomes.

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Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus

Abstract: Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

Cited by 219 publications

References 38 publications

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Low grade dysplasia in Barrett’s esophagus: Should we worry?

Detection of dysplasia in Barrett’s oesophagus: Are there impending optical and spectroscopic solutions?

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