Published in:
01-02-2009 | Hepatobiliary and Pancreatic Tumors
Immunohistochemically Detected Expression of p27Kip1 and Skp2 Predicts Survival in Patients with Intrahepatic Cholangiocarcinomas
Authors:
Nozomi Hashimoto, MD, Shinichi Yachida, MD, Keiichi Okano, MD, Hisao Wakabayashi, MD, Katsumi Imaida, MD, Kazutaka Kurokohchi, MD, Tsutomu Masaki, MD, Hisoka Kinoshita, MD, Masahiro Tominaga, MD, Tetsuo Ajiki, MD, Yonson Ku, MD, Takehiro Okabayashi, MD, Kazuhiro Hanazaki, MD, Makoto Hiroi, MD, Sadanobu Izumi, MD, Shohei Mano, MD, Setsuo Okada, MD, Yukihiko Karasawa, MD, Takashi Maeba, MD, Yasuyuki Suzuki, MD
Published in:
Annals of Surgical Oncology
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Issue 2/2009
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Abstract
In intrahepatic cholangiocarcinomas (ICCs), the prognostic significance of p27Kip1, a cyclin-dependent kinase inhibitor, remains controversial, and there have been no studies of degradation pathway associated proteins, S-phase kinase-interacting protein (Skp2), and Jun activation domain-binding protein-1 (Jab1). In the present study of 74 patients with ICC–mass forming type (ICC-MF) undergoing radical surgery, we determined immunohistochemical expression of p27Kip1, Skp2, and Jab1 and examined relationships with clinicopathologic findings and patient survival. On the basis of the average of labeling indices, we set cutoff values to define high and low expressors and divided the cases into two groups. A statistically significant correlation was found between low p27Kip1 expression and lymph node metastasis (P = .009). Patient survival in the low p27Kip1 expression group (n = 25) was also significantly worse than that in the high p27Kip1 expression group (n = 49, P = .0007). A significant inverse correlation was found between p27Kip1 and Skp2 expression (P = .016). High Skp2 expression (n = 36) was significantly associated with poor prognosis (P = .0046). High Jab1 expression was observed in 32 cases, but there was no statistically significant relationship with clinicopathologic findings or patient survival. The multivariate analysis revealed that low p27Kip1 and high Skp2 expression are independent and significant factors of poor prognosis. The results suggest that low p27Kip1 and high Skp2 expression are associated with aggressive tumor behavior, and these cell-cycle regulators are useful markers to predict outcome of patients with ICC-MF.