title: Lymphatic microvessel density is an independent prognostic factor in colorectal cancer.
abstract: OBJECTIVE
  Although lymph node metastasis via lymphatic vessels often is related with an adverse outcome, it is not well known whether lymphatic spread to lymph node needs the development of the new lymphatic formation. In addition, the correlation between lymphangiogenesis and prognosis has not been well documented. This study was designed to assess the prognostic value of lymphangiogenesis and lymphatic vessel invasion in colorectal cancer.
  
  
  METHODS
  We examined 106 colorectal cancer specimens by immunostaining for podoplanin, lymphatic endothelial specific marker. We evaluated lymphangiogenesis, as measured by lymphatic microvessel density, and lymphatic vessel invasion. We next investigated the association of these two parameters with the clinicopathologic findings and prognosis.
  
  
  RESULTS
  A significant correlation was observed between high lymphatic microvessel density and positive lymphatic vessel invasion (P = 0.0003). Positive lymphatic vessel invasion was significantly associated with the presence of lymph node metastasis (P = 0.0071). The survival curves demonstrated that both high lymphatic microvessel density and positive lymphatic vessel invasion were correlated with an adverse outcome (P = 0.0004 and P = 0.009, respectively). In a univariate analysis, high lymphatic microvessel density and positive lymphatic vessel invasion were negatively associated with the overall survival (P = 0.0011 and P = 0.0118, respectively). Furthermore, high lymphatic microvessel density, but not lymphatic vessel invasion, correlated with a poor outcome in a multivariate analysis (P = 0.0114).
  
  
  CONCLUSIONS
  Our data suggested that lymphatic vessel invasion was related with lymph node metastasis and that both lymphatic microvessel density and lymphatic vessel invasion were related with an adverse outcome in colorectal cancer. Furthermore, lymphatic microvessel density may be a useful prognostic factor in colorectal cancer.
authors.affiliation: Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Inoue
authors.forename: Noritaka
authors.initials: N
authors.lastname: Minagawa
authors.forename: Takefumi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shibao
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tsurudome
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome