A metastatic signature in entire lung adenocarcinomas irrespective of morphological heterogeneity
A metastatic signature in entire lung adenocarcinomas irrespective of morphological heterogeneity
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DOI：
10.1016/j.humpath.2006.11.019
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发表时间：
2007-05-01
期刊：
影响因子：
3.3
通讯作者：
Ishikawa, Yuichi
中科院分区：
文献类型：
--
作者：
Inamura, Kentaro;Shimoji, Takashi;Ishikawa, Yuichi
最近的微阵列表达研究支持这样的假设：转移潜力是在肿瘤发生的早期获得的，并且大多数肿瘤细胞具有转移的潜力。为了评估这种可能性，我们研究了侵袭性肺腺癌，其特征是表现出形态异质性，外围恶性程度较低，作为模型。在淋巴结阳性病变中，比较具有侵袭性外观的中度分化成分、具有较低恶性外观的外周分化良好成分以及患者匹配的淋巴结转移之间的基因表达谱。我们还将这些肿瘤与淋巴结阳性肺腺癌进行了比较，后者在形态学上与淋巴结阳性肿瘤无法区分。在原发性肿瘤和转移性肿瘤对之间观察到惊人的相似性，甚至在原发性分化良好的成分中也是如此。我们生成了一个 75 基因特征，根据淋巴结状态区分原发性肺腺癌。使用该基因集的分层聚类确定了一个由淋巴结阳性病例组成的独特独立组，与淋巴结阴性肿瘤和正常肺组织明显分开。结果表明，转移特征在整个进展过程中得以维持，这意味着整个原发肿瘤，包括形态学上恶性程度较低的成分，可能具有转移潜力。这一发现具有深远的临床意义。未来，可以通过活检来预测肿瘤的转移潜力，有助于避免对低风险患者进行不必要的淋巴结清扫。 (c) 2007 Elsevier Inc. 保留所有权利。
Recent microarray expression studies support the hypothesis that metastatic potential is acquired early in tumorigenesis and that most tumor cells have the potential to metastasize. To assess this possibility, we investigated invasive lung adenocarcinomas, which characteristically display morphological heterogeneity with a less malignant appearance at the periphery as a model. In lymph node-positive lesions, gene expression profiles were compared among moderately differentiated components with an aggressive appearance, peripheral well-differentiated components with a less malignant appearance, and patient-matched lymph node metastases. We also compared these with node-positive lung adenocarcinomas, which are morphologically indistinguishable from node-positive tumors. Striking similarities were observed between pairs of primary and metastatic tumors, even within primary well-differentiated components. We generated a 75-gene signature separating primary lung adenocarcinomas according to lymph node status. Hierarchical clustering using this gene set identified a distinct independent group composed of node-positive cases, clearly separate from node-negative tumors and normal lung tissue. The results suggest that the metastatic signature is maintained throughout progression, implying that the entirety of a primary tumor, including the morphologically less malignant components, might have metastatic potential. This finding has profound clinical implications. In the future, the metastatic potential of tumors may be predicted by biopsy, helping to avoid unnecessary lymph node dissection in low-risk patients. (c) 2007 Elsevier Inc. All rights reserved.