p21Waf1/Cip1 expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kip1, p53, or Rb

Background: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical ro les in cell cycle regulation and may influence the clinical behavior of tum ors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). Methods: Expression of p21, p27, p53, and Rb was studied by the immunohisto chemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. Results: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high e xpression groups for each protein. The 5-year survival rate for the high p2 1 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When pa tients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly differe nt (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node inv olvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were inde pendent prognostic factors, Conclusions: Expression of p21 is an independent prognostic factor in curat ively resected ESC. Definition of new subgroups of patients based on p21 ex pression may help to enhance the stratification of stage.