title: Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases.
abstract: OBJECTIVE
  The aim of this study was to investigate the use of D2-40 for the detection of lymphovascular invasion (LVI) in node positive and negative early breast cancer. LVI is associated with axillary lymph node metastases (ALNM) and a long-term prognostic factor. A precise identification of LVI would have a strong clinical impact for breast cancer patients.
  
  
  METHODS
  Immunohistochemical staining with D2-40 and CD34 was performed on formalin-fixed, paraffin-embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer. All slides were screened for the presence of LVI. Correlation with clinico-pathological factors including LVI as retrieved by routine haematoxylin and eosin (H.E.) stained sections and the eligibility for the prediction of ALNM was assessed.
  
  
  RESULTS
  Using the D2-40 antibody for immunostaining, our results demonstrate a significant higher detection (P < 0.001) of LVI as compared with routine H.E.-staining in early breast cancer. LVI was correctly identified by D2-40 (D2-40+) in 70 out of 254 tumors (28%) as compared to 40 tumors (16%) by routine HE staining (HE+). There was a significant correlation between D2-40 + LVI and age, t-stage, nodal status, grading and hormonreceptor-status. Correlation between D2-40 + LVI and menopausal-status, HER2-status and histological type was not significant, while there was a significant correlation of D2-40 and so called "triple negative" tumors (ER/PR and HER2neu-negative). In a multivariate analysis D2-40+ was the strongest predictor for ALNM with an odds ratio of 3.489 and a P-value of P = 0.0003, followed only by T-stage and grading with odds ratios of 3.167 and 1.953 and P-values P = 0.0003 and P = 0.0352.
  
  
  CONCLUSIONS
  Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H.E.-staining in early breast cancer. As LVI is a strong predictive and prognostic marker, the monoclonal antibody D2-40 has the potential to play a significant role in pathological routine workup of breast tumors. Further prospective studies are needed to prove the clinical impact of D2-40.
authors.affiliation: Department of Obstetrics and Gynecology, University of Bonn, Bonn, Germany. michael.braun@uni-bonn.de
authors.forename: Michael
authors.initials: M
authors.lastname: Braun
authors.forename: Uta
authors.initials: U
authors.lastname: Flucke
authors.forename: Manuel
authors.initials: M
authors.lastname: Debald
authors.forename: Gisela
authors.initials: G
authors.lastname: Walgenbach-Bruenagel
authors.forename: Klaus-Jürgen
authors.initials: KJ
authors.lastname: Walgenbach
authors.forename: Tobias
authors.initials: T
authors.lastname: Höller
authors.forename: Martin
authors.initials: M
authors.lastname: Pölcher
authors.forename: Matthias
authors.initials: M
authors.lastname: Wolfgarten
authors.forename: Axel
authors.initials: A
authors.lastname: Sauerwald
authors.forename: Mignon
authors.initials: M
authors.lastname: Keyver-Paik
authors.forename: Marietta
authors.initials: M
authors.lastname: Kühr
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008495:Medical Oncology / Q000379:methods; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin