Radiation Oncology, University Hospitals Leuven and Department of Oncology , KU Leuven, Leuven , Belgium.
Acta Oncol. 2013 Oct;52(7):1336-44. doi: 10.3109/0284186X.2013.813070. Epub 2013 Jul 23.
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.
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.
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).
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.
研究血液标志物是否可用于识别存在淋巴结转移的前列腺癌（PCa）患者。此外，还研究了上皮间质可塑性概念中的 E-钙黏蛋白表达。
本研究纳入了 75 例接受超扩展淋巴结清扫术和根治性前列腺切除术（RP）的局部临床 PCa 患者。47/75 例患者术前采用商业酶联免疫吸附试验检测血浆/血清中内皮素、转化生长因子-β1（TGF-β1）、骨桥蛋白、血管内皮生长因子（VEGF）、血管细胞黏附分子-1（VCAM-1）和 E-钙黏蛋白的水平，并与临床病理参数相关联。采用免疫组织化学分析检测诊断性活检（n=63）、RP 标本（n=75）和淋巴结转移（n=106）中 E-钙黏蛋白的表达。
隐匿性淋巴结转移几乎存在于半数患者（37/75）中，共有 106 个淋巴结受累。术前内皮素、TGF-β1、骨桥蛋白、VEGF、VCAM-1 和 E-钙黏蛋白水平与淋巴结状态均无显著相关性。仅发现血浆内皮素与血清前列腺特异性抗原之间存在正相关（Spearman r=0.44；p=0.002）。大多数活检（91.9%）和 RP 标本（79.7%）中 E-钙黏蛋白表达较强，而淋巴结中表达较弱（28.9%）。孤立肿瘤细胞（ITC）和微转移中的染色模式主要为同质，而大转移中则呈现出更为异质的模式（χ²，p<0.0001）。
在本研究中，未发现任何一种测试的血液标志物可用于 PCa 的淋巴结分期，组织中 E-钙黏蛋白的表达也不能用于分期。然而，ITC/微转移与大转移之间 E-钙黏蛋白表达模式的差异可能表明存在另一种生物学行为。大转移中特定的染色模式可能表明存在持续的上皮间质转化，这被认为是转移定植的一种机制。由于后者是转移过程中的限速步骤，因此评估 E-钙黏蛋白表达模式可能具有潜在的治疗意义。
