Absence of cyclooxygenase-2 protein expression is a predictor of tumor regression in rectal cancer treated with preoperative short-term chemoradiotherapy

Abstract

Purpose: Neoadjuvant chemoradiotherapy followed by total mesorectal excision has become the standard of care for patients with locally advanced rectal cancer. This study was designed to determine whether pretreatment cyclooxygenase-2 and p53 protein expression were predictors of histopathologic response in patients with rectal cancer treated with preoperative short-term chemoradiotherapy.

Methods: Fifty-two patients with low rectal cancer received short-term preoperative chemoradiotherapy (20 Gy given in 5 daily doses of 4 Gy and concurrent administration of Tegafur/Uracil 400 mg/day), followed by total mesorectal excision. Cyclooxygenase-2 and p53 protein expression were measured by immunohistochemistry before and at the time of resection. Tumor regression grading was evaluated according to the criteria by Rodel (Grade 4, complete regression; Grade 3, regression >50 percent; Grade 2, 25-50 percent; Grade 1,<25 percent; and Grade 0, no regression).

Results: Two patients had a pathologic complete response. Good response (Grade 3 + 4) was found in 57.7 percent of the resected specimens. Cyclooxygenase-2 was expressed in 80.8 percent of patients before chemoradiotherapy and in 100 percent after chemoradiotherapy. The rates of good response (Grade 3 + 4) were significantly associated with lack of cyclooxygenase-2 expression before chemoradiotherapy (P = 0.021). However, there was no correlation between p53 protein expression and tumor regression grading.

Conclusions: Patients with tumor lacking cyclooxygenase-2 expression before chemoradiotherapy are more likely to demonstrate good response to treatment. Cyclooxygenase-2 protein expression may be a marker for response to chemoradiotherapy in patients with rectal cancer.