Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Mod Pathol. 2011 Sep;24(9):1221-8. doi: 10.1038/modpathol.2011.82. Epub 2011 May 13.
Folate receptor alpha (FRα), encoded by folate receptor 1 (adult) gene, has emerged as a cancer biomarker and potential therapeutic target. In addition, its expression in tumors may offer prognostic information. The aim of this study was to assess the prognostic value of FRα expression and other common molecular markers in resected liver metastases from colorectal cancer. To maximize potential biological differences, we selected two groups of patients with markedly different outcomes as study subjects. Immunohistochemical analysis of FRα expression and other common markers (thymidylate synthase, p53, p27, BCL2, ki67, MLH1, MSH2 and MGMT) on tissue microarrays was carried out on samples from 160 patients; 56 patients survived at least 10 years following liver resection, and 104 died within 2 years of surgery. These markers were evaluated and compared with standard clinical predictors of outcome including a previously validated clinical risk score. Our results showed that in addition to known clinical risk factors, FRα positivity was significantly associated with the early death group (32% compared with 13%; P=0.03). None of the other common molecular markers were differentially expressed between the two groups. On multivariate analysis, clinical risk score, margin status and FRα expression were independently associated with outcome. Specific multivariate comparisons confirmed that FRα expression was associated with outcome independent of the clinical risk score and margin. These data demonstrate that FRα expression is present in a subset of resected hepatic colorectal cancer metastases, and this marker is independently associated with survival after hepatic resection. The prognostic value of FRα expression and the utility of FRα-targeted therapies in stage-IV colorectal cancer patients deserve further exploration.
叶酸受体α（FRα），由叶酸受体 1（成人）基因编码，已成为癌症生物标志物和潜在的治疗靶点。此外，其在肿瘤中的表达可能提供预后信息。本研究旨在评估 FRα 表达和其他常见分子标志物在结直肠癌切除肝转移中的预后价值。为了最大限度地体现潜在的生物学差异，我们选择了两组具有明显不同结局的患者作为研究对象。在组织微阵列上对 FRα 表达和其他常见标志物（胸苷酸合成酶、p53、p27、BCL2、ki67、MLH1、MSH2 和 MGMT）进行了免疫组织化学分析，样本来自 160 名患者；56 名患者在肝切除后至少存活 10 年，104 名患者在手术后 2 年内死亡。评估了这些标志物，并与包括先前验证的临床风险评分在内的标准临床预后预测因子进行了比较。我们的结果表明，除了已知的临床危险因素外，FRα 阳性与早期死亡组显著相关（32%比 13%；P=0.03）。两组之间没有其他常见分子标志物表达存在差异。多变量分析显示，临床风险评分、切缘状态和 FRα 表达与预后独立相关。具体的多变量比较证实，FRα 表达与预后相关，独立于临床风险评分和切缘。这些数据表明，FRα 表达存在于部分切除的肝结直肠癌转移灶中，该标志物与肝切除后的生存独立相关。FRα 表达的预后价值以及 FRα 靶向治疗在 IV 期结直肠癌患者中的应用价值值得进一步探讨。
