title: Clinicopathological significance of lymphangiogenesis and tumor lymphovascular invasion in indonesian breast cancers.
abstract: BACKGROUND
  Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalized tumor lymphovascular invasion (LVI). It also involves VEGF-C as the most important protein family. Lymphangiogenesis among breast cancer cases correlations with several clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and require clarification.
  
  
  OBJECTIVE
  To define correlations between VEGF-C expression, LVD and LVI with several clinicopathological parameters from Indonesian breast cancer patients.
  
  
  METHODS
  Using a cross-sectional study, a total of 48 paraffin-embedded tissues of breast cancer from Dr. Sardjito General Hospital Indonesia were assessed for VEGF-C expression, LVD and LVI by immunohistochemistry. Correlations of these markers with clinicopathological parameters like patient age, tumor size, lymph node status, grade, ER/PR and Her-2 status, cell proliferation and p-53 expression were investigated by linear analysis. Correlations of VEGF-C expression and LVI with several clinicopathological parameters were analyzed with Coefficient Contingency Chi-Square test.
  
  
  RESULTS
  The mean of patients age was 53.0 year, pre and post-menopausal patients accounting for 56.3% and 43.8%, respectively. Some 10.4% were well, 41.7% moderate and 47.9% poorly differentiated. ER positivity was evident in 50% while PR and Her-2 positivity was found in 31.3% and 33.3%, respectively. Breast cancer cells with over-expression of p-53 was 64.6% and with high cell proliferation was 56.3%. Lymph node metastasis was noted in 63.5%, and LVI in 72.9%. Significant correlations were found between LVD and tumor size (p:0.037), grade (p:0.000), lymphnode status (p:0.036), LVI (p:0.003), as well as with p-53 and cell proliferation. There were also significant correlation of VEGF-C (p:0.011) and LVI (p:0.001) with tumor grade. Only ER status was found to have a correlation with tumor size (p:0.027).
  
  
  CONCLUSIONS
  This study suggested that in Indonesian breast cancer patients, lymphangiogenesis is correlated with tumor size, grade, lymph node status and tumor lymphovascular invasion, the latter also being related with p-53 over expression and high cell proliferation.
authors.affiliation: Department of Anatomical Pathology, Faculty of Medicine, Gadjah Mada University, Jogjakarta, Indonesia. irianiwatiwidodo@yahoo.com
authors.forename: Irianiwati
authors.initials: I
authors.lastname: Widodo
authors.forename: Paranita
authors.initials: P
authors.lastname: Ferronika
authors.forename: Ahmad
authors.initials: A
authors.lastname: Harijadi
authors.forename: Fx Ediati
authors.initials: FE
authors.lastname: Triningsih
authors.forename: Totok
authors.initials: T
authors.lastname: Utoro
authors.lastname: Soeripto
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007214:Indonesia; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D042601:Lymphatic Vessels / Q000098:blood supply* / Q000473:pathology; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D042582:Vascular Endothelial Growth Factor C; C467486:VEGFC protein, human; C508053:ERBB2 protein, human