Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy
Background: 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. Objective: To investigate which type of marker to use and whether molecular detection...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | European Urology Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266616832200739X |
| _version_ | 1818016904546091008 |
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| author | Berna C. Özdemir Nicolas Arnold Achim Fleischmann Janine Hensel Irena Klima Marianna Kruithof-de Julio Fiona Burkhard Stefanie Hayoz Bernhard Kiss George N. Thalmann |
| author_facet | Berna C. Özdemir Nicolas Arnold Achim Fleischmann Janine Hensel Irena Klima Marianna Kruithof-de Julio Fiona Burkhard Stefanie Hayoz Bernhard Kiss George N. Thalmann |
| author_sort | Berna C. Özdemir |
| collection | DOAJ |
| description | Background: 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. Objective: To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence. Design, setting, and participants: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: Molecular detection of epithelial cell markers increases the number of positive LNs and predicts tumor recurrence already at surgery. Patient summary: 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. |
| first_indexed | 2024-04-14T07:19:39Z |
| format | Article |
| id | doaj.art-390591a70cd84e918683f6c868a654d9 |
| institution | Directory Open Access Journal |
| issn | 2666-1683 |
| language | English |
| last_indexed | 2024-04-14T07:19:39Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Urology Open Science |
| spelling | doaj.art-390591a70cd84e918683f6c868a654d92022-12-22T02:06:12ZengElsevierEuropean Urology Open Science2666-16832022-10-0144110Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical ProstatectomyBerna C. Özdemir0Nicolas Arnold1Achim Fleischmann2Janine Hensel3Irena Klima4Marianna Kruithof-de Julio5Fiona Burkhard6Stefanie Hayoz7Bernhard Kiss8George N. Thalmann9Urological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, Switzerland; Department of Oncology, University of Bern, Inselspital, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandInstitute of Pathology, University of Bern, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandSwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, SwitzerlandUrological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, Switzerland; Corresponding author. Department of Urology, University of Bern, Anna-Seiler Haus, Inselspital, CH-3010 Bern, Switzerland. Tel. +41 31 632 36 64; Fax: +41 31 632 21 80.Background: 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. Objective: To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence. Design, setting, and participants: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: Molecular detection of epithelial cell markers increases the number of positive LNs and predicts tumor recurrence already at surgery. Patient summary: 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.http://www.sciencedirect.com/science/article/pii/S266616832200739XProstate cancerLymph nodesMetastasisExtended lymphadenectomyMicrometastasisIsolated tumor cells |
| spellingShingle | Berna C. Özdemir Nicolas Arnold Achim Fleischmann Janine Hensel Irena Klima Marianna Kruithof-de Julio Fiona Burkhard Stefanie Hayoz Bernhard Kiss George N. Thalmann Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy European Urology Open Science Prostate cancer Lymph nodes Metastasis Extended lymphadenectomy Micrometastasis Isolated tumor cells |
| title | Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy |
| title_full | Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy |
| title_fullStr | Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy |
| title_full_unstemmed | Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy |
| title_short | Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy |
| title_sort | prediction of biochemical recurrence based on molecular detection of lymph node metastasis after radical prostatectomy |
| topic | Prostate cancer Lymph nodes Metastasis Extended lymphadenectomy Micrometastasis Isolated tumor cells |
| url | http://www.sciencedirect.com/science/article/pii/S266616832200739X |
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