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Published on: August 19, 2021
Identification and characterization of nodal metastases in prostate cancer patients at high risk for lymph node
Sofie Isebaert1, Karin Haustermans, Laura Van den Bergh
1Radiation Oncology, University Hospitals Leuven and Department of Oncology , KU Leuven, Leuven , Belgium.
Aim:
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.
Material And 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).
Conclusion:
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.
