Recent molecular biological studies suggested certain molecular markers might be useful as prognostic factors in patients with colorectal cancer. The purpose of this study was to investigate whether cyclin dependent inhibitor kinase p21WAF1/CIP1 (p21), p53 expression, and/or the presence of apoptosis had prognostic value in predicting survival in patients with advanced middle and lower rectal cancer who were treated with preoperative radio-chemotherapy. We examined the immunohistochemical expression of p21 and p53, and determined the degree of apoptosis in resected middle and lower rectal cancers from patients who received preoperative radio-chemotherapy (irradiation group, n=40) and from those who did not receive treatment (control group, n=35). The preoperative total radiotherapy dose was 42.6 Gy and the chemotherapy tegafur suppository dose was 750 mg/day. Clinicopathological features, and tumor expression of p53 and p21 and degree of apoptosis were analyzed by means of multivariate analysis. In the irradiation group, tumors were positive for p53, p21 and apoptosis in 34 of 40 (85.0%), 23 of 40 (57.5%) and 25 of 40 (62.5%) cases, respectively. The expression of p21 and the apoptotic index were significantly higher in the irradiated group compared to controls (2.0 versus 1.2%, p=0.05; 8 versus 3%, p=0.03, respectively). There was a significant correlation between p21 immunoreactivity and the degree of muscularis propria invasion (p=0.004), as well as between p21 immunoreactivity and survival rate (p=0.03). Multivariate analysis revealed that p21 expression (RR, 0.09; 95% CI, 0.01-0.78; p=0.03) and lymph node metastasis (RR, 3.63; 95% CI, 1.06-12.37; p=0.04) were significant prognostic factors for patient survival. These data suggested that p21 expression has prognostic value in predicting patient survival in advanced middle and lower rectal cancer.

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