Department of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
Surg Today. 2010 Mar;40(3):245-50. doi: 10.1007/s00595-009-4028-3. Epub 2010 Feb 24.
The liver is the most common site of metastasis in patients with colorectal cancer (CRC), and this is a determinant of the prognosis. However, no reliable molecular predictors of liver metastasis have yet been identified.
Sixty-two surgical specimens of colorectal cancer were studied. The first group included 25 patients who achieved a disease-free survival period of at least 6 years (CRC-M0), and the second group included 37 patients with synchronous (n = 22) or metachronous (n = 15) liver metastasis (CRC-M1). SMAD4, p53, and Ki-67 expression levels were assessed immunohistochemically.
The loss of SMAD4 expression and elevated Ki-67 expression were found significantly more frequently in CRC-M1 patients than in CRC-M0 patients (P = 0.0047 and P = 0.013, respectively). Statistically significant differences were also observed between the CRC-M0 group and the metachronous metastasis group. No difference was seen in the overexpression of p53 between the groups. A combination analysis of SMAD4 and Ki-67 revealed no cases with maintained levels of SMAD4 and a low Ki-67 expression had or developed liver metastasis.
The loss of SMAD4 expression and elevated Ki-67 expression was therefore found to significantly correlate with liver metastasis, regardless of the time of occurrence, thus indicating these factors to be predictive markers for liver metastasis in patients with CRC.
肝脏是结直肠癌（CRC）患者最常见的转移部位，也是决定预后的因素。然而，目前尚未发现可靠的肝转移分子预测因子。
研究了 62 例结直肠癌手术标本。第一组包括 25 例无疾病生存时间至少 6 年的患者（CRC-M0），第二组包括 37 例同时性（n=22）或异时性（n=15）肝转移患者（CRC-M1）。采用免疫组织化学法评估 SMAD4、p53 和 Ki-67 的表达水平。
CRC-M1 患者中 SMAD4 表达缺失和 Ki-67 表达升高的频率明显高于 CRC-M0 患者（P=0.0047 和 P=0.013）。CRC-M0 组与异时性转移组之间也存在统计学差异。两组之间 p53 的过表达无差异。SMAD4 和 Ki-67 的联合分析显示，没有同时维持 SMAD4 水平和低 Ki-67 表达的病例发生或发展为肝转移。
SMAD4 表达缺失和 Ki-67 表达升高与肝转移显著相关，无论发生时间如何，表明这些因素是 CRC 患者肝转移的预测标志物。
