Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance
Folate receptor-α expression in resectable hepatic colorectal cancer metastases: patterns and significance
复制标题
DOI：
10.1038/modpathol.2011.82
复制
发表时间：
2011-09-01
期刊：
影响因子：
7.5
通讯作者：
Shia, Jinru
中科院分区：
文献类型：
--
作者：
D'Angelica, Michael;Ammori, John;Shia, Jinru
叶酸受体 α (FR α) 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，它在肿瘤中的表达可能提供预后信息。本研究的目的是评估 FR α 表达和其他常见分子标记物在结直肠癌切除肝转移中的预后价值。为了最大化潜在的生物学差异，我们选择了两组结果明显不同的患者作为研究对象。对 160 名患者的样本进行组织微阵列上 FR α 表达和其他常见标志物（胸苷酸合酶、p53、p27、BCL2、ki67、MLH1、MSH2 和 MGMT）的免疫组织化学分析； 56 名患者在肝切除后存活了至少 10 年，104 名患者在手术后 2 年内死亡。对这些标志物进行了评估，并与结果的标准临床预测因子（包括先前验证的临床风险评分）进行了比较。我们的结果显示，除了已知的临床危险因素外，FR α 阳性与早期死亡组显着相关（32% 与 13%；P=0.03）。两组之间没有其他常见分子标记存在差异表达。在多变量分析中，临床风险评分、边缘状态和 FR α 表达与结果独立相关。特定的多变量比较证实 FR α 表达与独立于临床风险评分和边缘的结果相关。这些数据表明，FRα表达存在于切除的肝结直肠癌转移的子集中，并且该标记物与肝切除后的存活率独立相关。 FR α 表达的预后价值以及 FR α 靶向治疗在 IV 期结直肠癌患者中的效用值得进一步探索。现代病理学(2011) 24, 1221-1228; doi:10.1038/modpathol.2011.82； 2011 年 5 月 13 日在线发布
Folate receptor alpha (FR alpha), 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 FR alpha 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 FR alpha 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, FR alpha 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 FR alpha expression were independently associated with outcome. Specific multivariate comparisons confirmed that FR alpha expression was associated with outcome independent of the clinical risk score and margin. These data demonstrate that FR alpha 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 FR alpha expression and the utility of FR alpha-targeted therapies in stage-IV colorectal cancer patients deserve further exploration. Modern Pathology (2011) 24, 1221-1228; doi:10.1038/modpathol.2011.82; published online 13 May 2011