Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation

Carlson, Nicole; Lechago, Juan; Richter, Joel E.; Sampliner, Richard E.; Peterson, Leif E.; Santella, Regina M.; Goldblum, John R.; Falk, Gary W.; Ertan, Atilla; Younes, Mamoun

doi:10.1111/j.1572-0241.2002.05770.x

Cited by 32 publications

(13 citation statements)

References 20 publications

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“…Long-term follow up of patients in the randomized controlled LOTUS trial will hopefully provide us with more information on the influence of surgical vs. medical acid suppression on outcomes in BE (51). Curiously, Carlson et al (52) showed that acid suppression reduced oxidative damage in p53 negative, but not p53 positive biopsies arguing that once genetically unstable clones develop, acid suppression may be ineffective. Thus, timing of acid suppression may be important.…”

Section: Predictors Of Progression In Barrett’s Esophagusmentioning

confidence: 99%

Predictors of Progression in Barrett's Esophagus: Current Knowledge and Future Directions

Prasad

Bansal

Sharma

et al. 2010

American Journal of Gastroenterology

107

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Barrett’s esophagus is the strongest risk for esophageal adenocarcinoma (EAC), a malignancy with persistently poor long-term outcomes. EAC is thought to develop through progression of metaplasia to dysplasia to invasive carcinoma. Identification of factors predicting progression to EAC would help in focusing surveillance, chemoprevention or ablation at those deemed to be at highest risk of progression. We performed a comprehensive review of the literature and summarized current evidence on risk factors for progression in subjects with known BE. Clinical and demographic factors (age, male gender, length of BE segment) are associated with modestly increased odds of progression to EAC in some studies. Biomarkers such as aneuploidy and p53 loss of heterozygosity have been associated with increased risk of progression to high-grade dysplasia and / or EAC in single center prospective cohort studies. Promising newer techniques and markers have been recently reported with the potential to help risk stratify BE subjects. Development of a comprehensive BE risk progression score comprised of both clinical and biomarker variables should be the ultimate goal and can be achieved by multicenter prospective collaborative efforts. Though challenging, creation of such a score has the potential to improve outcomes and make the management of patients with BE more cost effective.

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Section: Predictors Of Progression In Barrett’s Esophagusmentioning

confidence: 99%

Predictors of Progression in Barrett's Esophagus: Current Knowledge and Future Directions

Prasad

Bansal

Sharma

et al. 2010

American Journal of Gastroenterology

107

View full text Add to dashboard Cite

show abstract

“…Thus far, the data on whether acid suppression is a useful chemopreventive strategy are conflicting. [112][113][114] The use of varying acid-suppression regimens and the lack of data from large prospective randomised trials make it difficult to evaluate their role. Laboratory and epidemiological data suggest that aspirin and non-steroidal anti-inflammatory drugs may be chemopreventive through their inhibitory effect on COX2.…”

Section: Tailored Therapy and Chemopreventionmentioning

confidence: 99%

Molecular basis of Barrett's oesophagus and oesophageal adenocarcinoma

Fitzgerald

2006

Gut

120

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“…Many p53 mutations are thought to arise by oxidative damage to cytosine bases in exons 5 to 8 (26). Acid suppressive therapies may decrease oxidative DNA damage, although preceding p53 mutations seem to prevent this reduction (27). Many of these mutations encode changes that stabilize the protein, preventing its breakdown and thereby leading to increased levels of mutant p53 within the cell.…”

Section: Mechanisms Of P53 Loss Of Functionmentioning

confidence: 99%

Clinical Use of p53 in Barrett's Esophagus

Keswani¹,

Noffsinger

Waxman³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Barrett's esophagus is an established precursor to esophageal adenocarcinoma. Whereas most patients with Barrett's esophagus do not progress to adenocarcinoma, patients with progression have a poor prognosis. Current management strategies use frequent endoscopic surveillance and multiple nontargeted biopsies. This approach, however, may miss dysplastic areas. Furthermore, given the relatively high prevalence of Barrett's esophagus but low incidence of progression, this invasive and expensive approach has not been shown to be cost-effective. Thus, there is intense interest in using biomarkers to identify patients at increased risk of progressing to adenocarcinoma. This has included examination of mutations in the tumor suppressor gene, p53. In this report, we discuss the biology of p53 and the incidence of p53 mutations in Barrett's esophagus and review relevant studies regarding the ability of p53 to predict neoplastic progression. Additionally, we report our results of the expression of p53 by immunohistochemistry in a group of 18 patients that have undergone endoscopic esophageal mucosal resection for dysplasia. Although the presence of a p53 mutation increases the risk of neoplastic progression, the absence of this mutation does not abrogate the risk. Continuing efforts, therefore, are needed to define and prospectively validate a panel of biomarkers to risk-stratify patients with Barrett's esophagus. Determination of p53 mutational status may ultimately be a component of such a panel. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1243 -9)

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Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation

Cited by 32 publications

References 20 publications

Predictors of Progression in Barrett's Esophagus: Current Knowledge and Future Directions

Predictors of Progression in Barrett's Esophagus: Current Knowledge and Future Directions

Molecular basis of Barrett's oesophagus and oesophageal adenocarcinoma

Clinical Use of p53 in Barrett's Esophagus

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