CIRCULATING ANTI-P53 ANTIBODIES IN ESOPHAGEAL CANCER-PATIENTS ARE FOUND PREDOMINANTLY IN INDIVIDUALS WITH P53 CORE DOMAIN MUTATIONS IN THEIR TUMORS

Serum antibodies reacting with the tumor suppressor protein p53 have b een detected previously in cancer patients with a variety of neoplasms , Two initial (although insufficient) prerequisites for a B-cell respo nse to occur have been proposed: p53 protein accumulation in the tumor or a mutant p53 gene, or both. We have examined 65 esophageal cancer cases (42 from Guangzhou and Shenyang, People's Republic of China, and 23 from Paris, France) to obtain a prevalence estimate of anti-pb3 an tibodies for this type of cancer and to define the relationship of p53 tumor status to B-cell immune response, Sera were analyzed in a tripl icate assay (enzyme-linked immunoassay, immunoprecipitation, and immun oblot) for anti-p53 antibodies, Tumor DNA was screened for mutations i n exons 5-8, and tumor tissue was examined by immunohistochemistry for abnormal p53 protein accumulation, p53 mutations were found in 36 (58 %) of 62 cases analyzed. Sixteen patients (25%) had circulating antibo dies to the tumor suppressor protein, All but two (88%) of the tumors from seropositive cases had a mutation in the DNA binding region of th e p53 gene, and with one exception, these tumors also showed nuclear a ccumulation of the p53 protein, In contrast, tumor mutations were foun d in just 22 (46%) of the 48 individuals in whom we did not detect ant i-p53 antibodies. Among the 22 seronegative cases for which we found n o tumor mutations, 11 revealed pig protein accumulation by immunohisto chemical analysis. Thus, circulating anti-p53 antibodies may be presen t in one-fourth of esophageal cancer patients, most of whom also would be expected to have a p53 gene mutation in their tumors, Patients wit hout such mutations appear considerably less likely to mount a B-cell response to the p53 tumor suppressor protein than those that do (P < 0 .01).