Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer

• Published in: Clinical cancer research 1996-10, Vol.2 (10), p.1767-1775
• Main Authors: TRIVERS, G. E, DE BENEDETTI, V. M. G, MILLER, R. D, HARRIS, C. C, CAWLEY, H. L, CARON, G, HARRINGTON, A. M, BENNETT, W. P, JETT, J. R, COLBY, T. V, TAZELAAR, H, PAIROLERO, P
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies - blood; Antibodies, Neoplasm - blood; Biological and medical sciences; Case-Control Studies; DNA Mutational Analysis; Female; Humans; Immunoblotting; Immunoenzyme Techniques; Immunohistochemistry; Lung Diseases, Obstructive - blood; Lung Diseases, Obstructive - immunology; Male; Medical sciences; Middle Aged; Mutation; Neoplasms - blood; Neoplasms - diagnosis; Neoplasms - immunology; Pneumology; Polymorphism, Single-Stranded Conformational; Precipitin Tests; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Tumor Suppressor Protein p53 - analysis; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - immunology; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265

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.