title: Detection of lymphovascular invasion by D2-40 (podoplanin) immunoexpression in endometrial cancer.
abstract: BACKGROUND
  Lymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40-based LVI evaluation for the prediction of lymph node metastases and patients' outcome.
  
  
  METHODS
  Immunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed.
  
  
  RESULTS
  Immunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40-negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%).
  
  
  CONCLUSIONS
  D2-40-based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.
authors.affiliation: Department of Gynecology and Obstetrics, Center of Integrated Oncology, University Hospital Bonn, Bonn, Germany.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Weber
authors.forename: Axel
authors.initials: A
authors.lastname: Sauerwald
authors.forename: Martin
authors.initials: M
authors.lastname: Pölcher
authors.forename: Michael
authors.initials: M
authors.lastname: Braun
authors.forename: Manuel
authors.initials: M
authors.lastname: Debald
authors.forename: Nuran Bektas
authors.initials: NB
authors.lastname: Serce
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Giesela
authors.initials: G
authors.lastname: Brunagel-Walgenbach
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000098853:Podoplanin
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin; C500987:monoclonal antibody D2-40