title: Histopathological features predict metastatic potential in locally advanced colon carcinomas.
abstract: BACKGROUND
  Metastatic dissemination can exist before a pathologically and clinically detectable manifestation. The structural heterogeneity of colon cancer (CC) in histological sections with respect to the morphology of tumor aggressiveness and composition of the tumor microenvironment raises the question of whether the microscopical tumor architecture enables a discrimination of groups with different metastatic potential. This would result in an assessment of the prognosis and provision of an ancillary tool for the therapeutic management after surgery, beside the estimation of the local tumor extent.
  
  
  METHODS
  In order to identify predictive biomarkers for metastasis of locally advanced CC, which can easily be integrated into the pathologist's daily routine diagnostic activity, we determined tumor budding, peritumoral inflammation, extent of desmoplasia and necrosis, density of macro- and microvascular blood vessels and functional state of lymphatics in the tumor center, invasive margin and tumor-free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic, subserosa-invasive CC.
  
  
  RESULTS
  Features influencing nodal metastasis in the univariate analysis included high tumor budding (p = 0.004), high large vessel density in the subserosa (p = 0.043), abundant desmoplasia (p = 0.049), non-finger-like desmoplastic pattern (p = 0.051) and absent lymphocellular intratumoral inflammation (p = 0.084). In the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p = 0.023, p = 0.017, p = 0.037, p = 0.012, respectively) with a good discrimination ability (AUC of 0.853). Features associated with distant metastasis in the univariate analysis included high tumor budding (p = 0.002), low intratumoral small vessel density (p = 0.013), absent lymphocellular intratumoral inflammation (p = 0.048) and abundant necrosis (p = 0.073). In the multivariate analysis only tumor budding was an independent predictor for haematogenous metastasis (p = 0.007) with a good discrimination ability (AUC of 0.829).
  
  
  CONCLUSIONS
  Thus, mainly tumor budding but also the described structural characteristics of the peritumoral tissue appears to reflect the metastatic potential of locally advanced CC and therefore should be stated in pathological reports.
authors.affiliation: Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. c.jayasinghe@gmx.de.|Department of Pathology, Laboratory Medicine Cologne, Geibelstr. 2, 50931, Cologne, Germany. c.jayasinghe@gmx.de.
authors.forename: Caren
authors.initials: C
authors.lastname: Jayasinghe
authors.affiliation: Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. simiantonaki@yahoo.de.|Institute of Pathology Essen-Mitte, Am Deimelsberg 34a, 45276, Essen, Germany. simiantonaki@yahoo.de.
authors.forename: Nektaria
authors.initials: N
authors.lastname: Simiantonaki
authors.affiliation: Institute of Pathology, Johannes Gutenberg University, Langenbeckstr. 1, 55101, Mainz, Germany. kirkpatrick@uni-mainz.de.
authors.forename: Charles James
authors.initials: CJ
authors.lastname: Kirkpatrick
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001808:Blood Vessels / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D019408:Platelet Endothelial Cell Adhesion Molecule-1