Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer

Resistance to chemotherapy remains a serious problem inhibiting the success ful treatment of advanced esophageal cancer. A number of studies have revea led that p53 genetic alteration and protein overexpression can predict chem osensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conduc ted to examine whether analysis of serum p53 Abs could predict the chemosen sitivity of esophageal cancer. Serum analysis of p53 antibodies was perform ed by enzyme-linked immunosorbent assay in 19 patients with esophageal squa mous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues we re also analyzed for chemosensitivity by the histoculture drug response ass ay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5- FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 pr otein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibi tion index of patients positive for p53-Abs was significantly lower than th at of patients negative for p53-Abs (P < 0.001). This tendency was also obs erved in the inhibition index to 5-FU. The presence of serum p53-Abs was as sociated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, t he detection of serum p53-Abs is suggested to be useful for predicting chem osensitivity in patients with esophageal cancer.