Pretreatment CD133 and cyclooxygenase-2 expression as the predictive markers of the pathological effect of chemoradiotherapy in rectal cancer patients.

Abstract

CD133 confers chemoradioresistance properties to cells and has recently been used to identify cancer-initiating cells. We investigated whether the overexpression of CD133 and cyclooxygenase-2 can be used as predictive markers of tumor response to preoperative chemoradiotherapy in patients with rectal cancer. The study was conducted at the National Defense Medical College Hospital in Japan. We recruited 96 patients who underwent a single regimen of preoperative short-term chemoradiotherapy (20 Gy in 5 fractions with 400 mg/day Tegafur/Uracil for 1 week) and radical resection. This was a retrospective study. We obtained pretreatment biopsy specimens of these patients and immunostained these specimens with antibodies for CD133, cyclooxygenase-2, p53, p27, p21, and epidermal growth factor receptor. The resected primary tumor was evaluated according to 2 different tumor regression grading systems that were based on the degrees of fibrosis and cytological alterations. Positivity for CD133 or cyclooxygenase-2 expression was associated with chemoradioresistance, which was determined by the degree of fibrosis, in both univariate (P = .02 and P = .0003) and multivariate (P = .03 and P = .001) analyses. Univariate and multivariate analyses of the degree of cytological alterations also revealed a significant association between chemoradioresistance and the expression of CD133 (P = .005 and P = .003) and cyclooxygenase-2 (P = .005 and P = .03), whereas other markers failed to associate. The information on patients' outcome was not available. Our study revealed the independent predictive values of CD133 and cyclooxygenase-2 expressions in histological tumor regression after preoperative chemoradiotherapy.