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

Induction chemoradiotherapy before esophagectomy for esophageal carcinoma s eems to improve patient survival. Given the toxicity of this regimen, it wo uld 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 evaluat ing the relationship between p53 expression and chemoradiosensitivity in hu man tissues. We immunohistochemically evaluated p53 protein expression in 9 5 biopsy specimens from patients with esophageal carcinoma before chemoradi otherapy, p53 expression was correlated to the pathologic response identifi ed 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+, greater than or equal to 76%. Pathologic response in esophagectomy specimens was categorized as overt residual tumor (ORT), mini mal residual tumor, and no residual tumor. Of the 95 patients, 64 had adeno carcinoma, and 31 had squamous cell carcinoma. Of those with adenocarcinoma , 46 (72%) of 64 were positive for p53. Thirty-seven (80%) of 46 p53+ patie nts had ORT, compared with 4 (22%) of 18 p53- patients (P < .001). There wa s no correlation between the degree of p53 staining and pathologic response . Of those with squamous cell carcinoma, 13 (42%) of 18 were positive for p 53. Three (23%) of 13 p53+ patients had ORT, compared with 4 (22%) of 18 p5 3+ 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 ex ists in patients with esophageal squamous cell carcinoma.