Potential application of p53 as an intermediate biomarker in Barrett's esophagus

Jones, David R.; Davidson, Ann G.; Summers, Carol L.; Murray, Gordon F.; Quinlan, Dennis C.

doi:10.1016/0003-4975(94)90551-7

Cited by 49 publications

(20 citation statements)

References 19 publications

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“…Most of the markers that have been 7,12,20,29,38,41,6 Of these, p53 has been the most extensively studied. The p53 gene is rarely mutated in non-dysplastic GI epithelium (<5%), but the frequency of mutations increases dramatically in HGD and ACA in both BE and IBD.…”

Section: Discussionmentioning

confidence: 99%

AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease

Dorer

Odze

2006

American Journal of Surgical Pathology

121

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Alpha-methylacyl-CoA racemase (AMACR) catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters, and is overexpressed in a variety of neoplasms, such as prostate and colon cancer. The aim of this study was to evaluate AMACR expression in the metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus (BE), ulcerative colitis (UC), and Crohn's disease (CD) and to determine whether its expression can be used to detect dysplastic epithelium in these conditions. One hundred thirty-four routinely processed biopsy and/or resection specimens from 134 patients with BE [M/F ratio: 5.7, mean age: 67 y (36 negative (intestinal metaplasia only), 14 indefinite for dysplasia (IND), 16 low-grade dysplasia (LGD), 32 high-grade dysplasia (HGD), and 36 invasive adenocarcinoma (ACA)] and 74 specimens from 74 patients with inflammatory bowel disease (IBD) [56 with ulcerative colitis, 18 with Crohn's disease, M/F ratio: 1.8, mean age: 55 y (17 negative, 7 IND, 26 LGD, 10 HGD, and 14 ACA)] were immunostained with a monoclonal AMACR antibody (p504S). The degree of cytoplasmic staining in all cases was evaluated in a blinded fashion according to the following grading system: 0, negative (0% cells positive); 1+, 1% to 10% cells positive; 2+, 10% to 50% cells positive; or 3+, >50% cells positive. In patients with BE, AMACR was not expressed in any negative foci (0%) but was significantly increased (P<0.0001) in foci of LGD (38%), HGD (81%), and ACA (72%). Three of 14 (21%) IND foci from 3 BE patients were only focally positive (grade 1: 7%, 2: 14%). However, 1 of these 3 patients had follow-up information available and had developed ACA subsequently. Similarly, in patients with IBD, AMACR was not expressed in any foci considered negative for dysplasia, but was significantly increased (P<0.0001) in foci of LGD (96%), HGD (80%), and ACA (71%). Only 1/7 (14%) IND focus from 1 patient was focally positive (grade 1). The sensitivity for the detection of LGD and HGD in BE and IBD was 38% and 81%, and 96% and 80%, respectively, for the 2 types of disorders. The specificity was 100% for both BE and IBD. AMACR is involved in the neoplastic progression in BE and IBD. The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions.

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Section: Discussionmentioning

confidence: 99%

AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease

Dorer

Odze

2006

American Journal of Surgical Pathology

121

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“…Although many biomarkers have been proposed for stratification of cancer risk in BE, few are sufficiently selective to segregate dysplastic Barrett's epithelium, and few have been shown to be predictive of progression to esophageal adenocarcinoma [24]. P53 attracted significant interest in the recent past as an immunohistochemical marker associated with dysplasia in BE [25][26][27]. However, high rates of false negatives and false positives, in comparison to p53 gene aberrations and lack of standardization of the technique, hamper the use of p53 immunohistochemistry in practice [2,28,29].…”

Section: Discussionmentioning

confidence: 99%

Expression of α-methylacyl–coenzyme A racemase in dysplastic Barrett's epithelium

2006

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“…Multiple early studies showed that p53 overexpression is increased as histology progresses from metaplasia to high-grade dysplasia and to adenocarcinoma (45)(46)(47). Later studies showed that esophagectomy specimens containing adenocarcinoma with overexpression of p53 had adjacent dysplastic epithelium overexpressing p53 (48,49).…”

Section: Studies Of P53 and Barrett's Esophagusmentioning

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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Potential application of p53 as an intermediate biomarker in Barrett's esophagus

Cited by 49 publications

References 19 publications

AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease

AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease

Expression of α-methylacyl–coenzyme A racemase in dysplastic Barrett's epithelium

Clinical Use of p53 in Barrett's Esophagus

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