title: Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis.
abstract: BACKGROUND
  Immunohistochemical studies of lymphatic vessels have been limited by a lack of specific markers. Recently, the novel D2-40 antibody, which selectively marks endothelium of lymphatic vessels, was released. The aim of our study is to compare lymphatic and blood vessel invasion detected by hematoxylin and eosin (H&E) versus that detected by immunohistochemistry, relating them with morphologic and molecular prognostic factors.
  
  
  METHODS
  We selected 123 cases of invasive mammary carcinomas stratified into three subgroups according to axillary lymph node status: macrometastases, micrometastases, and lymph node negative. Lymphatic (LVI) and blood (BVI) vessel invasion were evaluated by H&E and immunohistochemistry using the D2-40 and CD31 antibodies, and related to histologic tumor type and grade, estrogen and progesterone receptors, E-cadherin, Ki67, p53, and Her2/neu expression.
  
  
  RESULTS
  LVI was detected in H&E-stained sections in 17/123 cases (13.8%), and in D2-40 sections in 35/123 cases (28.5%) (Kappa = 0.433). BVI was detected in H&E-stained sections in 5/123 cases (4.1%), and in CD31 stained sections in 19/123 cases (15.4%) (Kappa = 0.198). LVI is positively related to higher histologic grade (p = 0.013), higher Ki67 expression (p = 0.00013), and to the presence of macrometastases (p = 0.002), and inversely related to estrogen (p = 0.0016) and progesterone (p = 0.00017) receptors expression.
  
  
  CONCLUSIONS
  D2-40 is a reliable marker of lymphatic vessels and is a useful tool for lymphatic emboli identification in immunostained sections of breast carcinomas with higher identification rates than H&E. Lymphatic vessel invasion was related to other features (high combined histologic grade, high Ki67 score, negative hormone receptors expression) associated with worse prognosis, probable reflecting a potential for lymphatic metastatic spread and aggressive behavior.
authors.affiliation: Departamento de Anatomia Patológica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. vanessa.zschaber@gmail.com
authors.forename: Vanessa F Z
authors.initials: VF
authors.lastname: Marinho
authors.forename: Konradin
authors.initials: K
authors.lastname: Metze
authors.forename: Fernanda S F
authors.initials: FS
authors.lastname: Sanches
authors.forename: Gislene F S
authors.initials: GF
authors.lastname: Rocha
authors.forename: Helenice
authors.initials: H
authors.lastname: Gobbi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D001365:Axilla; D014408:Biomarkers, Tumor / Q000032:analysis; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000175:diagnosis / Q000556:secondary*; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D042601:Lymphatic Vessels / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis*; D009363:Neoplasm Proteins / Q000032:analysis; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; C031192:oncofetal antigens