Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma

Purpose: Alterations in the cell cycle regulatory cyclin/retinoblastoma pro tein (pRB) pathway play a important role in tumor progression in esophageal squamous cell carcinoma (ESCC). In the present study, we evaluated the pro gnostic significance of the combined analysis of cyclin D1 and pRB in ESCC retrospectively. Methods: Immunoreactivities of cyclin D1 and pRB were eval uated in 148 surgically resected ESCC by use of monoclonal antibodies. Dise ase-free survival of patients was compared among the four subgroups accordi ng to the phenotypes of cyclin DI and pRB expressions. Results: High immuno reactivities of pRB and cyclin D1 were detected in 64.2% and 40.5% of tumor s, respectively. The loss of pRB expression and overexpression of cyclin D1 correlated with short survival. However, these factors were not detected a s independently prognostic in multivariate analysis. In 107 surviving patie nts who underwent curative operation, co-expressed pRB and cyclin D1 (pRB /cyclin D1 +: 29 patients) were correlated with unfavorable prognosis (dis ease-free 5-year survival rate: 42.7%) and high cancer recurrence rate (44. 8 %) compared with that of 40 patients with pRB + / cyclin D1- tumors (70.5 % and 27.5%). The disease-free 5-year survival rate of patients with pRB+/c yclin D1-tumors was significantly better than that of other groups (P = 0.0 01). However, the disease-free 5-year survival rate of 29 patients with pRB + /cyclin D1 +: tumors was equivalent to that of 29 patients with pRB-/cyc lin D1-tumors (48.3%), and that of nine patients with pRB-/ cyclin D1+ tumo rs (22.2%, P=0.237). Conclusions: Our results suggest that overexpression o f cyclin D1 may suppress pRB function. and that combined analysis of pRB an d cyclin D1 may be a useful parameter of patient prognosis in ESCC.