Deregulation of G1/S transition is a common event in carcinoma of the ampulla of vater.
OBJECTIVE
Aberrant expression of cell cycle regulators and subsequent deregulation of G1/S transition is one of the most important characteristics of human cancer. The aim of this study was to determine the overall pattern of deranged expression of the cell cycle regulators involved in the G1/S transition in ampullary carcinoma.


METHODS
Using immunohistochemistry, we investigated the expression of p21WAF1/CIP1, p27Kip1, p16INK4, cyclin D1, cyclin E, pRb and p53 in 14 resected specimens of ampullary carcinoma and defined the proliferative activity of each tumor by quantifying Ki-67 antigen.


RESULTS
Decreased expression of p21WAF1/CIP1, p27Kip1, and p16INK4 was detected in 6 (43%), 11 (79%), and 4 (29%) tumors, respectively. Four tumors (29%) overexpressed cyclin D1 and 8 (57%) overexpressed cyclin E. Eight tumors (57%) overexpressed pRb. Aberrant accumulation of p53 was observed in 10 (71%) of the tumors. Overall, the expression of two or more of these cell cycle regulators was altered in all of the 14 tumors. Decreased p21WAF1/CIP1 expression was related to higher TMN stage (P = 0.04) and lymphatic invasion (P = 0.04). The proliferative index was higher in tumors with decreased p27Kip expression (P = 0.005), and in tumors with cyclin E overexpression (P = 0.06).


CONCLUSIONS
Our observations suggest that deregulation of G1/S transition is a very common event in ampullary carcinoma, and that altered expression of cell cycle regulators is associated with the aggressive behavior of this tumor. Correcting the G1/S transition regulatory machinery may provide a novel therapy for this malignancy.
Li
Xin
X
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hui
Ai-Min
AM
Shi
Ya-Zhou
YZ
Sun
Lin
L
Takayama
Tadatoshi
T
Makuuchi
Masatoshi
M
D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater; D003138:Common Bile Duct Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016196:S Phase / Q000502:physiology*
C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen