title: A metastatic signature in entire lung adenocarcinomas irrespective of morphological heterogeneity.
abstract: 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-negative 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.
authors: Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo, Japan.
authors: Kentaro
authors: K
authors: Inamura
authors: Takashi
authors: T
authors: Shimoji
authors: Hironori
authors: H
authors: Ninomiya
authors: Miyako
authors: M
authors: Hiramatsu
authors: Michiyo
authors: M
authors: Okui
authors: Yukitoshi
authors: Y
authors: Satoh
authors: Sakae
authors: S
authors: Okumura
authors: Ken
authors: K
authors: Nakagawa
authors: Tetsuo
authors: T
authors: Noda
authors: Masashi
authors: M
authors: Fukayama
authors: Yuichi
authors: Y
authors: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction