title: Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers.
abstract: BACKGROUND
  We have previously described an alternative invasion-independent pathway of cancer metastasis in a murine mammary tumor model. This pathway is initiated by intravasation of tumor nests enveloped by endothelial cells of sinusoidal vasculature within the tumor. In this study, we examined whether evidence for the invasion-independent pathway of metastasis is present in human cancers.
  
  
  METHODS
  Archival specimens of 10 common types of human cancers were examined for the presence of sinusoidal vasculature enveloping tumor nests and subsequently generated endothelial-covered tumor emboli in efferent veins.
  
  
  RESULTS
  A percentage of tumor emboli in all cancers was found to be enveloped by endothelial cells, but these structures were particularly prevalent in renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. A common feature of the vasculature in these tumors was the presence of dilated sinusoid-like structures surrounding tumor nests. A high mean vascular area within tumors, an indication of sinusoidal vascular development, was significantly related to the presence of endothelial-covered tumor emboli.
  
  
  CONCLUSIONS
  These results suggest that an invasion-independent metastatic pathway is possible in a wide variety of human cancers. Further investigation of this phenomenon may present new therapeutic strategies for the amelioration of cancer metastasis.
authors.affiliation: Department of Pathology, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan. sugino@fmu.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugino
authors.forename: Tomiko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Go
authors.initials: G
authors.lastname: Ogura
authors.forename: Atsuko
authors.initials: A
authors.lastname: Saito
authors.forename: Takeaki
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hoshi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yoshida
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D004617:Embolism / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology