Immunohistochemically Detected Expression of p27Kip1 and Skp2 Predicts Survival in Patients with Intrahepatic Cholangiocarcinomas
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- 作者：Nozomi Hashimoto MD (1) (2)
Shinichi Yachida MD (1)
Keiichi Okano MD (1)
Hisao Wakabayashi MD (1)
Katsumi Imaida MD (2)
Kazutaka Kurokohchi MD (3)
Tsutomu Masaki MD (3)
Hisoka Kinoshita MD (4)
Masahiro Tominaga MD (4)
Tetsuo Ajiki MD (4)
Yonson Ku MD (4)
Takehiro Okabayashi MD (5)
Kazuhiro Hanazaki MD (5)
Makoto Hiroi MD (6)
Sadanobu Izumi MD (7)
Shohei Mano MD (8)
Setsuo Okada MD (9)
Yukihiko Karasawa MD (10)
Takashi Maeba MD (10)
Yasuyuki Suzuki MD (1) - 刊名：Annals of Surgical Oncology
- 出版年：2009
- 出版时间：February 2009
- 年：2009
- 卷：16
- 期：2
- 页码：395-403
- 全文大小：417KB
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Shinichi Yachida MD (1)
Keiichi Okano MD (1)
Hisao Wakabayashi MD (1)
Katsumi Imaida MD (2)
Kazutaka Kurokohchi MD (3)
Tsutomu Masaki MD (3)
Hisoka Kinoshita MD (4)
Masahiro Tominaga MD (4)
Tetsuo Ajiki MD (4)
Yonson Ku MD (4)
Takehiro Okabayashi MD (5)
Kazuhiro Hanazaki MD (5)
Makoto Hiroi MD (6)
Sadanobu Izumi MD (7)
Shohei Mano MD (8)
Setsuo Okada MD (9)
Yukihiko Karasawa MD (10)
Takashi Maeba MD (10)
Yasuyuki Suzuki MD (1)
1. Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan
2. Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan
3. Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan
4. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medical Sciences, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
5. Department of Surgery, Kochi Medical School, Kohasu-Okocho, Nankoku-city, Kochi, 783-8505, Japan
6. Department of Pathology, Kochi Medical School, Kohasu-Okocho, Nankoku-city, Kochi, 783-8505, Japan
7. Department of Surgery, Kagawa Prefectural Central Hospital, 5-4-16 Ban-cho, Takamatsu-city, Kagawa, 760-8557, Japan
8. Department of Pathology, Kagawa Prefectural Central Hospital, 5-4-16 Ban-cho, Takamatsu-city, Kagawa, 760-8557, Japan
9. Department of Surgery, Sakaide City Hospital, 1-6-43 Bunkyo-cho, Sakaide-city, Kagawa, 762-0031, Japan
10. Department of Surgery, Social Insurance Ritsurin Hospital, 3-5-9 Ritsurin-cho, Takamatsu-city, Kagawa, 760-0073, Japan
文摘
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.