title: Identification and characterization of nodal metastases in prostate cancer patients at high risk for lymph node involvement.
abstract: OBJECTIVE
  To investigate whether blood-based markers could be used to identify prostate cancer (PCa) patients harboring lymph node (LN) metastases. In addition, E-cadherin expression was studied within the concept of epithelial mesenchymal plasticity.
  
  
  METHODS
  Seventy-five patients with clinically localized PCa who underwent a superextended lymphadenectomy followed by radical prostatectomy (RP) were included in this study. Preoperative plasma/serum levels of endoglin, transforming growth factor-β1 (TGF-β1), osteopontin, vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were measured using commercially available enzyme immunoassays in 47/75 patients and correlated with clinicopathological parameters. E-cadherin expression in the diagnostic biopsies (n = 63), RP specimens (n = 75) and LN metastases (n = 106) was examined by immunohistochemical analysis.
  
  
  RESULTS
  Occult LN metastases were present in almost half of the patients (37/75), with a total of 106 affected LN. Preoperative levels of endoglin, TGF-β1, osteopontin, VEGF, VCAM-1 nor E-cadherin were significantly associated with LN status. Only a positive correlation between plasma endoglin and serum prostate-specific antigen was found (Spearman's r = 0.44; p = 0.002). The majority of biopsies (91.9%) and RP specimens (79.7%) showed strong E-cadherin expression, while in the LN this was found to be much weaker (28.9%). While the staining pattern in the isolated tumor cells (ITC) and micrometastases was mainly homogenous, the macrometastases showed a much more heterogeneous pattern (χ², p < 0.0001).
  
  
  CONCLUSIONS
  In this study, none of the blood-based markers tested could be used for nodal staging in PCa, nor could E-cadherin expression in the tissue. However, the difference in E-cadherin expression pattern between the ITC/micrometastases and the macrometastases may point to another biological behavior. The specific staining pattern seen in the macrometastases could indicate an ongoing mesenchymal epithelial transition, presumed to be a mechanism for metastatic colonization. As the latter is the rate-limiting step in the metastatic process, evaluation of the E-cadherin expression pattern could have potential therapeutic implications.
authors.affiliation: Radiation Oncology, University Hospitals Leuven and Department of Oncology , KU Leuven, Leuven , Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Isebaert
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.forename: Laura
authors.initials: L
authors.lastname: Van den Bergh
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.forename: Piet
authors.initials: P
authors.lastname: Dirix
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.forename: Christophe M
authors.initials: CM
authors.lastname: Deroose
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000556:secondary* / Q000601:surgery; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor