Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Oncol Rep. 2012 Jul;28(1):161-71. doi: 10.3892/or.2012.1797. Epub 2012 May 4.
Reduced expression of Raf-1 kinase inhibitor protein (RKIP) has been documented in a number of human malignancies, including colorectal carcinoma (CRC). However, despite the importance of hepatic colorectal metastasis (HCM) for the prognosis of CRC patients, no studies have been conducted regarding RKIP expression in HCM tissues or its prognostic significance. The aim of this study was to clarify the relationship between reduced RKIP expression and HCM and to identify independent predictors for recurrent HCM, which will ultimately help identify patients at high risk of developing metastatic recurrence. An immunohistochemical study of RKIP expression was performed using primary CRC and/or corresponding HCM tissue samples obtained from 117 patients. Forty-nine of these patients did not harbor HCM and 68 harbored HCM. RKIP expression was reduced in 24.5% (12/49) of CRCs without HCM, 47.1% (32/68) of CRCs with HCM and 67.6% (46/68) of HCM. This distribution of RKIP downregulation was statistically significant. RKIP expression was found to independently predict recurrent HCM, with a higher relative risk (6.661) compared to that of nodal metastasis (4.690). A reduction of RKIP expression in HCM was a significant predictor of poor prognosis. The median survival of patients with reduced RKIP expression was 35 months, compared with more than 10 years in patients with positive RKIP expression. Multivariate survival analysis demonstrated that RKIP expression in HCM was an independent predictor of overall survival, with a hazard ratio of 5.161, a value comparable to the risk associated with advanced TNM stage (5.247). We demonstrated that a reduction of RKIP expression in HCM had an independent predictive value for metastatic recurrence and less favorable clinical outcomes in patients with HCM. Our results strongly suggest that patients harboring HCM with reduced RKIP expression require careful monitoring after hepatic resection to detect potentially resectable metastatic recurrences.
RKIP 在多种人类恶性肿瘤中表达降低，包括结直肠癌（CRC）。然而，尽管肝转移是 CRC 患者预后的重要因素，但尚未对 HCM 组织中的 RKIP 表达及其预后意义进行研究。本研究旨在阐明 RKIP 表达降低与 HCM 的关系，并确定 HCM 复发的独立预测因子，最终有助于识别发生转移性复发风险较高的患者。采用免疫组化方法检测了 117 例 CRC 患者的原发 CRC 及/或相应 HCM 组织样本中 RKIP 的表达情况。其中 49 例患者无 HCM，68 例患者存在 HCM。在无 HCM 的 CRC 中，RKIP 表达降低的比例为 24.5%（12/49），有 HCM 的 CRC 中为 47.1%（32/68），HCM 中为 67.6%（46/68）。这种 RKIP 下调的分布具有统计学意义。RKIP 表达独立预测 HCM 复发，其相对风险（6.661）高于淋巴结转移（4.690）。HCM 中 RKIP 表达降低是预后不良的显著预测因子。RKIP 表达降低的患者中位生存时间为 35 个月，而 RKIP 表达阳性的患者超过 10 年。多变量生存分析表明，HCM 中 RKIP 表达是总生存的独立预测因子，危险比为 5.161，与晚期 TNM 分期（5.247）相关的风险相当。我们证实，HCM 中 RKIP 表达降低对 HCM 患者的转移复发具有独立预测价值，且临床结局较差。我们的研究结果强烈表明，存在 RKIP 表达降低的 HCM 患者在肝切除后需要密切监测，以发现可能可切除的转移性复发。
