Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer.
Serum anti-p53 antibodies (p53-Abs) may be surrogate markers for both p53 alterations and preclinical cancer. Ancillary to a prospective trial to abate progressive development of clinical stages of chronic obstructive pulmonary disease, we conducted a retrospective, nested case-control study. Twenty-three cases were diagnosed with cancer during the trial. Enzyme immunoassay, immunoblotting, and immunoprecipitation were used to detect p53-Abs in serum, immunohistochemistry (IHC) to detect p53 accumulation, and single-strand conformation polymorphism and DNA sequencing to detect p53 mutations in tumor samples. p53-Abs were detected by three types of assays in five (23%) of the cancer patients, 80% of whom had detectable p53-Abs before diagnosis: 2 lung cancers (7 and 6 months before), 1 prostate cancer (11 months), and 1 breast cancer (5 months). Four Ab-positive patients had IHC-positive tumors. Two of 4 Ab-positive patients and 2 of 14 Ab-negative had p53 missense mutations or base pair deletion and IHC-positive tumors. The 44 noncancer COPD controls, matched with the cancer cases for age, gender, and smoking habits, were negative for p53-Abs. These results indicate that p53-Abs may facilitate the early diagnosis of cancer in a subset of smokers with chronic obstructive pulmonary disease who are at an increased cancer risk.
Trivers
G E
GE
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. triversg@intra.nci.nih.gov
De Benedetti
V M
VM
Cawley
H L
HL
Caron
G
G
Harrington
A M
AM
Bennett
W P
WP
Jett
J R
JR
Colby
T V
TV
Tazelaar
H
H
Pairolero
P
P
Miller
R D
RD
Harris
C C
CC
D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D000912:Antibodies, Neoplasm / Q000097:blood; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D018807:Polymorphism, Single-Stranded Conformational; D011233:Precipitin Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D000912:Antibodies, Neoplasm; D016159:Tumor Suppressor Protein p53