Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis.
OBJECTIVE
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.
Cawley
H M
HM
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA.
Meltzer
S J
SJ
De Benedetti
V M
VM
Hollstein
M C
MC
Muehlbauer
K R
KR
Liang
L
L
Bennett
W P
WP
Souza
R F
RF
Greenwald
B D
BD
Cottrell
J
J
Salabes
A
A
Bartsch
H
H
Trivers
G E
GE
D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D001471:Barrett Esophagus / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D004247:DNA / Q000032:analysis; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000906:Antibodies; D016159:Tumor Suppressor Protein p53; D004247:DNA