Concomitant analysis of p16/INK4, cyclin D1, and retinoblastoma protein expression in esophageal squamous cell carcinoma

BACKGROUND/AIMS: Cyclin D1 expression is one of the important biologic factors and its close association with p16/INK4 and retinoblastoma protein expression has been proven in patients with esophageal squamous cell carcinoma, however, the clinical implication of these associations is still unknown. The objective of this study is to clarify its clinical significance. METHODOLOGY: We studied p16, cyclin D1, and pRB expression using immunohistochemistry in the resected specimens of 156 patients who underwent curative esophagectomy. RESULTS: Alteration of p16 expression, positive cyclin D1 expression and loss of pRB expression were demonstrated in 108 (69%) patients, 47 (30%) patients, and 48 (31%) patients, respectively. An inverse correlation was found between p16 expression and pRB expression (P < 0.0001). Of 47 cyclin D1-positive tumors, 39 (83%) tumor exhibited alteration of p16 and 43 (92%) tumors were positive for pRB. Based on p16, cyclin D1, and pRB expression, 138 (88%) patients were divided into the following three groups: p16-/cyclin D1+/pRB+ (n = 44), p16+/cyclin D1-/pRB- (n = 38), p16-/cyclin D1-/pRB+ (n = 56). The three groups were the most influential prognostic factors in a Cox's proportional regression model. The p16-/cyclin D1+/pRB+ group had frequent hematogenous recurrence, while the other groups had frequent lymph node recurrence. CONCLUSIONS: Assessment of p16, cyclin D1, and pRB expression may be helpful for determining postoperative therapeutic strategies in patients with esophageal squamous cell carcinoma.