title: Cutaneous breast cancer deposits show distinct growth patterns with different degrees of angiogenesis, hypoxia and fibrin deposition.
abstract: OBJECTIVE
  We postulated that skin metastases and cutaneous local recurrences from breast adenocarcinoma show different growth patterns with distinct angiogenic profiles.
  
  
  RESULTS
  Fifty-one surgically resected dermal breast cancer deposits were evaluated for growth pattern, E-cadherin expression, presence of necrosis and a fibrotic focus, fibrin deposition, carbonic anhydrase IX expression (CA IX), microvessel density, endothelial cell proliferation and blood vessel immaturity. Growth patterns were infiltrative, with carcinoma cells infiltrating the dermis without significant disturbance of the pre-existing architecture, expansive, meaning that a nodule of carcinoma cells and desmoplastic tissue pushed aside the pre-existing dermal structures, or mixed. All lobular carcinomas showed an infiltrative growth and lacked membranous E-cadherin expression. Different growth patterns in the ductal carcinomas were not correlated with differences in E-cadherin expression. The presence of necrosis and/or a fibrotic focus and the expression of the hypoxia marker CA IX were significantly associated with an expansive growth. Fibrin was present in all expansive deposits and less frequently in the other growth patterns. There was a positive association between fibrin deposition, CA IX expression and microvessel density. The latter was significantly higher in the expansive and mixed growth patterns than in the infiltrative pattern. Endothelial cell proliferation was highest in the expansive growth pattern and was positively correlated with the presence of a fibrotic focus and with fibrin deposition. The maximum percentage of immature blood vessels was higher in the expansive and mixed growth patterns than in the infiltrative one.
  
  
  CONCLUSIONS
  The recognition of different subgroups of cutaneous breast cancer deposits with different degrees of hypoxia-driven angiogenesis may have important implications for the usefulness of anti-angiogenic therapy.
authors.affiliation: Department of Pathology, University Hospital Antwerp, B-2650 Edegem, Belgium. cecile.colpaert@uza.be
authors.forename: C G
authors.initials: CG
authors.lastname: Colpaert
authors.forename: P B
authors.initials: PB
authors.lastname: Vermeulen
authors.forename: P
authors.initials: P
authors.lastname: Van Beest
authors.forename: A
authors.initials: A
authors.lastname: Soubry
authors.forename: G
authors.initials: G
authors.lastname: Goovaerts
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
authors.forename: E A
authors.initials: EA
authors.lastname: Van Marck
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D015687:Cell Hypoxia; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000098:blood supply / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015820:Cadherins; D009363:Neoplasm Proteins; D005337:Fibrin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases