Cell cycle-regulated factors in esophageal cancer.

Alterations of cell cycle-regulated genes play an important role in the process of carcinogenesis, and some of them are thought to be prognostic factors in esophageal cancer. The expressions of p53, p16, pRB and Cyclin D1 proteins were evaluated immunohistochemically in 144 patients who underwent curative esophagectomy without any adjuvant therapy before surgery. p53 overexpression was observed in 99 (69%) out of the 144 patients. No significant correlation was noted between p53 and any other gene expression. p16 expression was observed in 12 (8.3%) out of all cases. A negative correlation was recognized between p16 and Cyclin D1 expression (P=0.0004). pRB expression was observed in 130 (90.3%) out of all cases, whereas pRB expression was not observed in 11 out of the 12 patients with p16-positive tumors. A negative correlation was also found between p16 and pRB (P < 0.0001). A positive correlation was noted between pRB and Cyclin D1 expression (P=0.0009). The cumulative survival rate of patients without pRB expression was significantly lower than that of patients with positive expression (P=0.003). In the multivariate survival analysis, pRB expression was an independent prognostic factor. In 98% of all patients with esophageal cancer, impairment of the G1 checkpoint is due to a loss of function by p16, pRB or Cyclin D1, which showed a negative correlation in each factor. In addition, aberrant expression of pRB is useful as a prognostic factor in esophageal cancer.