Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India

Esophageal cancer (EC) in the Indian population presents in advanced stages with poor prognosis and warrants the identification of a non-invasive mark er for early detection and better prognostic assessment. We have previously reported high prevalence of p53 protein accumulation in esophageal squamou s-cell carcinomas (ESCCs). The present study was designed to determine (i) if esophageal cancer patients elicit a humoral immune response to intra-tum oral p53 protein accumulation and (ii) their relationship with p53 gene mut ations. The goal was to compare the cellular events, p53 protein accumulati on and gene mutations with the presence of serum anti-p53 antibodies (p53-A bs) and to assess the utility of serological p53-Ab analysis as a surrogate marker for p53 alterations in esophageal cancer. A high prevalence of circ ulating p53-Abs was observed in 36 of 60 (60%) ESCC patients. In a subset o f 44 ESCCs, exons 5-9 of the p53 gene were examined for mutations by PCR an d direct sequencing of PCR products. Mutational data have been correlated w ith p53-Abs and p53 protein accumulation in ESCCs. Circulating p53-Abs in E SCC patients were significantly associated with intra-tumoral p53 protein a ccumulation (p = 0.0005). A strong correlation observed between humoral imm une response against p53 protein, missense gene mutations and protein accum ulation warrants the application of serological p53-Abs as a non-invasive s urrogate marker in screening high-risk populations for early detection of m alignancy. (C) 2000 Wiley-Liss, Inc.