Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis

被引:68
作者
Cawley, HM
Meltzer, SJ
De Benedetti, VMG
Hollstein, MC
Muehlbauer, KR
Liang, L
Bennett, WP
Souza, RF
Greenwald, BD
Cottrell, J
Salabes, A
Bartsch, H
Trivers, GE
机构
[1] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Maryland, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21201 USA
[3] Baltimore Vet Affairs Hosp, Baltimore, MD USA
[4] German Canc Res Ctr, D-6900 Heidelberg, Germany
[5] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA
关键词
D O I
10.1016/S0016-5085(98)70360-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late-stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. Methods: We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. Results: p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. Conclusions: Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy.
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页码:19 / 27
页数:9
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