ALTERED P16 MTS1/CDKN2 AND CYCLIN D1/PRAD-1 GENE-EXPRESSION IS ASSOCIATED WITH THE PROGNOSIS OF SQUAMOUS-CELL CARCINOMA OF THE ESOPHAGUS/

The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively re gulate cyclin-dependent kinase 4-mediated phosphorylation of pRB in th e cell cycle of normal cells. p16/CDKN2 gene and cyclin D1/PRAD-1 gene alterations have been detected in squamous cell carcinoma cell lines and in several primary squamous cell carcinomas of the esophagus, We i mmunohistochemically assessed p16 and cyclin D1 expression in 111 squa mous cell carcinomas of the esophagus after evaluation of the antibodi es against p16 and cyclin D1 protein using four squamous cell carcinom a cell lines. Loss of p16 expression was detected in 56 of 111 cases ( 50%). The mean number of metastatic lymph nodes without p16 expression was significantly higher than the number of nodes with p16 expression (P = 0.04). The postoperative survival rate for patients without p16 expression was significantly lower than that of patients with p16 expr ession (P = 0.04). Cyclin D1 overexpression was found in 28 of the 111 cases (25%) and correlated with distant organ metastasis after curati ve surgery (P = 0.05). The survival rate of patients with cyclin D1 ov erexpression was significantly lower than that of patients without cyc lin D1 overexpression (P = 0.01). A positive correlation between the l oss of p16 expression and cyclin D1 overexpression was observed (P = 0 .03). The loss of p16 expression and overexpression of cyclin D1 may b e useful prognostic indicators in patients with squamous cell carcinom as of the esophagus. It may be possible to select more suitable treatm ent for patients with squamous cell carcinomas of the esophagus by eva luating the status of p16 and cyclin D1 expression.