Autoantibodies against P53 protein in patients with transitional cell carcinoma of the bladder.
Cellular accumulation and conformational changes of mutant p53 could act as immunogens for auto-antibodies (auto-Abs) generation when altered p53 from tumoral cells reaches the blood stream. Our main objective was to compare the presence and clinical implications of p53-antibodies in serum with the immunohistochemical (IHC) tissue overexpression of protein p53 in patients with transitional cell carcinoma of the bladder, evaluating their association with bladder cancer parameters and their prognostic value. The study comprised 59 patients with bladder cancer (group 1) and 15 healthy controls (group 2). Serum p53-Abs were measured by ELISA. Mutant p53 protein IHC overexpression was examined from paraffin embedded tissues using monoclonal DO-7 Ab. Serum p53-Abs were detected in 14/59 and IHC P53 was positive in 24/59 patients from group 1. All p53-Abs positive patients had IHC p53 positive tumors, but some patients with IHC positive immunoreactivity showed undetectable p53-Abs. None of the healthy controls had detectable p53-Abs. Titres of p53-Abs were associated with stage and grade. P53 overexpression was dependent on stage, grade, pattern of growth and focality. P53 Abs showed a significant prognostic value for disease free survival (p = 0.0059) and life expectancy (p < 0.0005) and for IHQ p53 for life expectancy (p = 0.0033). Patients with positive P53 Abs showed a higher probability for a shorter survival OR = 6.38 (1.77-22.99) than those who were positive for IHQ p53 OR = 4.00 (1.31-12.8) or those who were negative for p53 Abs and/or IHQ p53. The measurement of p53 Abs in serum appeared to be a simple determination which might reflect the p53 status and might help in the selection of those bladder cancer patients with a worse prognosis.
Sanchez-Carbayo
M
M
Laboratorio de Marcadores Tumorales, Hospital General Universitario de Alicante, Spain. mscarbayo@ibercom.com
Chulia
M T
MT
Niveiro
M
M
Aranda
I
I
Mira
A
A
Soria
F
F
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D016022:Case-Control Studies; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality
D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53