Overexpression of p53 protein associates decreased response to chemoradiotherapy in patients with esophageal carcinoma.

Induction chemoradiotherapy before esophagectomy for esophageal carcinoma seems to improve patient survival. Given the toxicity of this regimen, it would be useful to predict those patients likely to benefit. p53 is known to mediate apoptosis in response to DNA damage, but there are few data evaluating the relationship between p53 expression and chemoradiosensitivity in human tissues. We immunohistochemically evaluated p53 protein expression in 95 biopsy specimens from patients with esophageal carcinoma before chemoradiotherapy. p53 expression was correlated to the pathologic response identified in subsequent esophagectomy specimens. p53 immunoreactivity was recorded semiquantitatively using the following scale: neg, < 5%; 1+, 5-25%; 2+, 26-50%; 3+, 51-75%; 4+, > or = 76%. Pathologic response in esophagectomy specimens was categorized as overt residual tumor (ORT), minimal residual tumor, and no residual tumor. Of the 95 patients, 64 had adenocarcinoma, and 31 had squamous cell carcinoma. Of those with adenocarcinoma, 46 (72%) of 64 were positive for p53. Thirty-seven (80%) of 46 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P < .001). There was no correlation between the degree of p53 staining and pathologic response. Of those with squamous cell carcinoma, 13 (42%) of 18 were positive for p53. Three (23%) of 13 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P = .96). Our data indicate that overexpression of p53 protein is associated with decreased responsiveness to induction chemoradiotherapy in patients with esophageal adenocarcinoma but that no such association exists in patients with esophageal squamous cell carcinoma.