Suppressed MKP-1 Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma
Suppressed MKP-1 Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma
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DOI：
10.1159/000089766
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发表时间：
2005-11
期刊：
影响因子：
3.5
通讯作者：
E. Tsujita;A. Taketomi;T. Gion;Y. Kuroda;K. Endo;A. Watanabe;H. Nakashima;S. Aishima;S. Kohnoe;Y. Maehara
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文献类型：
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作者：
E. Tsujita;A. Taketomi;T. Gion;Y. Kuroda;K. Endo;A. Watanabe;H. Nakashima;S. Aishima;S. Kohnoe;Y. Maehara
目的：在多种体内肿瘤模型中，丝裂原激活蛋白激酶（MAPK）活性的增加与更恶性的表型相关。本研究旨在阐明手术切除的肝细胞癌 (HCC) 中 MKP-1 的表达。方法：我们回顾了 77 例未经术前治疗而接受初次肝切除术的 HCC 患者的病例。对石蜡包埋的组织进行 MKP-1 的免疫组织化学分析。研究了 MKP-1 表达与临床结果之间的相关性。结果：对肿瘤细胞进行免疫组织化学染色，检测 77 例 HCC 患者中 66 例（85%）的肿瘤细胞中 MKP-1 表达水平与正常肝细胞相同，而 11 例（15%）HCC 中 MKP-1 表达水平下降。 MKP-1 表达降低与血清甲胎蛋白水平和肿瘤大小显着相关 (p < 0.05)。 MKP-1 阴性和阳性患者的 5 年无病生存率分别为 0 和 31.0%（p < 0.01）。 MKP-1 阴性和阳性患者手术切除后 5 年生存率分别为 18.2% 和 65.5%（p < 0.01）。结论：HCC 中 MKP-1 的表达是 HCC 患者预后的独立预后因素。将来，探索磷酸酶表达是否可以解释针对 MAPK 激活的 HCC 治疗的反应将是有用的。
Objective: An increase in the activity of mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vivo. This study was designed to clarify the expression of MKP-1 in surgically resected hepatocellular carcinoma (HCC). Methods: We reviewed the cases of 77 patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on paraffin-embedded tissues. The correlation between MKP-1 expression and clinical outcome was investigated. Results: Tumor cells were immunohistochemically stained for MKP-1 expression, and the same levels as in normal hepatocytes were detected in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1 expression significantly correlated with serum α-fetoprotein levels and tumor size (p < 0.05). The disease-free survival rates in MKP-1-negative and -positive patients were 0 and 31.0% at 5 years, respectively (p < 0.01). The survival rates after a surgical resection in MKP-1-negative and -positive patients were 18.2 and 65.5% at 5 years, respectively (p < 0.01). Conclusions: The MKP-1 expression in HCC was an independent prognostic factor for outcome in HCC patients. In the future, it will be useful to explore whether the phosphatase expression might account for the response to HCC treatments targeting at MAPK activation.