The role of p27kip1 protein expression on the biological behavior of intrahepatic cholangiocarcinoma

Recent studies have reported that a decreased p27kip1 protein (p27) express ion is associated with aggressive tumor behavior in several human malignanc ies. In this study, we examined the role of p27 expression in intrahepatic cholangiocarcinoma (ICC) and the noncancerous intrahepatic bile duct epithe lium and assessed its association with clinicopathologic features, especial ly the influence of decreased p27 expression by the tumor on its prognosis as determined by immunohistochemistry. Almost all noncancerous bile duct ep ithelia show positive nuclear staining and reveal a faintly positive reacti on in the cytoplasm. In 62 surgically resected ICCs, a variable degree of p ositive p27 nuclear staining is recognized. A subset (13 of 62 cases; 21.0% ) of the carcinomas displayed cytoplasmic staining. We classified 62 cases into 2 groups, a low expression group ( < 50% of p27 nuclear positive cells ) and a high expression group (greater than or equal to 50% of p27 nuclear positive cells), and tested for the association between positive expression and clinicopathologic features. We found that a low expression of nuclear p27 was correlated with positive vascular invasion (P < .05). The survival curve of the group with low p27 nuclear expression was significantly lower than that of the group with high p27 nuclear expression (P < .005). Accordi ng to the multivariate analyses, low p27 expression can be considered an in dependent prognostic factor whose occurrence indicates a worse prognosis. W e conclude that a decreased p27 expression adds an independent parameter th at can be used when determining the prognosis of patients with ICC.