CIRCULATING P53 ANTIBODIES AS EARLY MARKERS OF ORAL-CANCER - CORRELATION WITH P53 ALTERATIONS

p53 aberrations are early events in the pathogenesis of betel- and tob acco-related oral malignancies. Accumulation of p53 protein in oral le sions may elicit a humoral immune response against p53 protein in thes e patients, p53 antibodies (Abs) were analyzed in 183 sera obtained fr om patients with premalignant or malignant oral lesions and normal ind ividuals by enzyme-linked immunoassay using recombinant p53 protein as antigen. These results were correlated with accumulation of p53 prote in in patients' matched oral tissue specimens. Circulating p53 Abs wer e observed in 24 of 70 (34%) cancer patients and 15 of 50 (30%) patien ts with premalignant oral lesions. p53 Abs showed a significant associ ation with increase in tumor size and dedifferentiation of tumors, fac tors indicative of poor prognosis. Expression of p53 protein was analy zed in 43 matched oral lesions (18 premalignant and 25 malignant cases ), All the p53-seropositive patients (7 leukoplakia and 11 squamous ce ll carcinoma) showed elevated levels of p53 protein in matched oral le sions. However, the total number of patients seropositive for p53 Abs was lesser than that of patients exhibiting p53 protein accumulation i n oral lesions. Four of the 63 normal healthy individuals who were hea vy consumers of tobacco (smoking/chewing) and betel were found to be p ositive for p53 Abs, Detection of circulating p53 Abs in patients with premalignant oral lesions suggests that humoral immune response again st p53 protein is an early event in oral oncogenesis and may be a surr ogate marker for both p53 alteration and preclinical cancer.