Alterations of retinoblastoma protein and p16INK4 protein expression in extrahepatic bile duct carcinomas.
OBJECTIVE
Human cancer development results from dysfunction of G1-phase regulators of the cell cycle. Retinoblastoma protein and p16INK4 are the most essential links between cell cycle control and cancer. We examined the expression of p16INK4 and pRb and their possible prognostic relevance in 34 extrahepatic bile duct carcinomas.


METHODS
Expression of pRb and p16INK4 was determined using immunohistochemical techniques. Associations between expression of pRb and p16INK4 and the clinicopathological features were analyzed by using the chi 2 test and survival analysis was performed by Log-rank test.


RESULTS
Two (6%) extrahepatic bile duct carcinomas were pRb negative, 26 (76%) showed pRb overexpression, and 6 (18%) demonstrated moderate expression. Twenty-two (65%) tumors were p16INK4 negative and 12 (35%) were p16INK4-positive. Cases with pRb-negative or pRb overexpression were significantly correlated with tumor progression (P = 0.004) and TNM stage (P = 0.009). Alterations in pRb and p16INK4 expression did not correlate with patient outcome.


CONCLUSIONS
Alterations of pRb and p16INK4 expression are frequently involved in extrahepatic bile duct carcinomas, and that aberrant pRb expression significantly associates with tumor progression.
Cui
X
X
Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
Hui
A M
AM
Li
X
X
Shi
Y Z
YZ
Takayama
T
T
Hatakeyama
K
K
Makuuchi
M
M
D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000737:chemistry / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D017734:Bile Ducts, Extrahepatic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000032:analysis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein