title: Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix.
abstract: OBJECTIVE
  We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated.
  
  
  METHODS
  We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40.
  
  
  RESULTS
  Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells.
  
  
  CONCLUSIONS
  Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal. longatto@ecsaude.uminho.pt
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
authors.forename: Sônia Maria Miranda
authors.initials: SM
authors.lastname: Pereira
authors.forename: Daniela
authors.initials: D
authors.lastname: Etlinger
authors.forename: Marise A R
authors.initials: MA
authors.lastname: Moreira
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Jubé
authors.forename: Geraldo Silva
authors.initials: GS
authors.lastname: Queiroz
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm / Q000032:analysis*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; C500987:monoclonal antibody D2-40; C031192:oncofetal antigens; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors