Molecular detection of lymph node (LN) micrometastases by analyzing mRNA expression of epithelial markers in prostate cancer (PC) patients provides higher sensitivity than histopathological examination.
To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence.
LN samples from PC patients undergoing radical prostatectomy with extended LN dissection between 2009 and 2011 were examined for the presence of micrometastases by both routine histopathology and molecular analyses.
The mRNA expression of a panel of markers of prostate epithelial cells, prostate stem cell-like cells, epithelial-to-mesenchymal transition, and stromal activation, was performed by quantitative real-time polymerase chain reaction. The expression levels of these markers in LN metastases from three PC patients were compared with the expression levels in LN from five control patients without PC in order to identify the panel of markers best suited for the molecular detection of LN metastases. The predictive value of the molecular detection of micrometastases for biochemical recurrence was assessed after a follow-up of 10 yr.
Prostate epithelial markers are better suited for the detection of occult LN metastases than molecular markers of stemness, epithelial-to-mesenchymal transition, or reactive stroma. An analysis of 1023 LNs from 60 PC patients for the expression of prostate epithelial cell markers has revealed different expression levels and patterns between patients and between LNs of the same patient. The positive predictive value of molecular detection of occult LN metastasis for biochemical recurrence is 66.7% and the negative predictive value is 62.5%. Limitations are sample size and the hypothesis-driven selection of markers.
Molecular detection of epithelial cell markers increases the number of positive LNs and predicts tumor recurrence already at surgery.
We show that a panel of epithelial prostate markers rather than single genes is preferred for the molecular detection of lymph node micrometastases not visible at histopathological examination.
European urology open science. 2022 Aug 16*** epublish ***
Berna C Özdemir, Nicolas Arnold, Achim Fleischmann, Janine Hensel, Irena Klima, Marianna Kruithof-de Julio, Fiona Burkhard, Stefanie Hayoz, Bernhard Kiss, George N Thalmann
Urological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, Switzerland., Institute of Pathology, University of Bern, Bern, Switzerland., Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, Switzerland.