Anne Offermann1, Doris Roth1, Marie Christine Hupe2, Silke Hohensteiner3, Finn Becker1, Vincent Joerg1, Jessica Carlsson4, Christiane Kuempers1, Julika Ribbat-Idel1, Lars Tharun1, Verena Sailer1, Jutta Kirfel1, Maria Svensson5, Ove Andren4, Verena Lubczyk3, Rainer Kuefer6, Axel S Merseburger2, Sven Perner7. 1. Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck, Germany; Pathology of the Research Center Borstel, Leibniz Lung Center, Borstel, Germany. 2. Department of Urology, University Hospital Schleswig-Holstein, Germany. 3. Department of Pathology, Klinik am Eichert Alb Fils Kliniken, Goeppingen, Germany. 4. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. 5. Department of Research and Education, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. 6. Department of Urology, Klinik am Eichert Alb Fils Kliniken, Goeppingen, Germany. 7. Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck, Germany; Pathology of the Research Center Borstel, Leibniz Lung Center, Borstel, Germany. Electronic address: sven.perner@uksh.de.
Abstract
INTRODUCTION: Simply applicable biomarkers for prostate cancer patients predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen receptor signaling and to correlate with an aggressive prostate cancer phenotype. Based on these data, we proofed TRIM24 as a prognostic biomarker for risk stratification. MATERIALS AND METHODS: We performed TRIM24 immunohistochemistry on 2 independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases, and 129 benign prostatic samples from 497 patients as well as on 246 prostate needle biopsies. Expression data were correlated with clinic-pathological data including biochemical recurrence-free survival (bRFS) as endpoint. RESULTS: Benign samples show no or low TRIM24 expression in 94%, while tumor tissues demonstrate significant higher levels. Strongest expression is observed in advanced and metastatic tumors. In multivariate analyses, TRIM24 up-regulation on radical prostatectomy specimens correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher grade group, positive nodal status and extraprostatic tumor growth. TRIM24 assessment on prostate needle biopsies taken prior to treatment decision at time of initial diagnosis significantly correlates with recurrence after surgery. CONCLUSION: Using 2 large independent radical prostatectomy specimen cohorts, we found that TRIM24 expression predicts patients' risk to develop disease recurrence with high accuracy and independent from other established biomarkers. Further, this is the first study exploring TRIM24 expression on prostate needle biopsies which represents the clinically relevant tissue type on which biomarkers guide treatment decisions. Thus, we strongly suggest introducing TRIM24 evaluation in prostate needle biopsies in clinical routine as an inexpensive and simple immunohistochemical test.
INTRODUCTION: Simply applicable biomarkers for prostate cancerpatients predicting the clinical course are urgently needed. Recently, TRIM24 has been identified to promote androgen receptor signaling and to correlate with an aggressive prostate cancer phenotype. Based on these data, we proofed TRIM24 as a prognostic biomarker for risk stratification. MATERIALS AND METHODS: We performed TRIM24 immunohistochemistry on 2 independent cohorts including a total of 806 primary tumors, 26 locally advanced/recurrent tumors, 30 lymph node metastases, 30 distant metastases, and 129 benign prostatic samples from 497 patients as well as on 246 prostate needle biopsies. Expression data were correlated with clinic-pathological data including biochemical recurrence-free survival (bRFS) as endpoint. RESULTS: Benign samples show no or low TRIM24 expression in 94%, while tumor tissues demonstrate significant higher levels. Strongest expression is observed in advanced and metastatic tumors. In multivariate analyses, TRIM24 up-regulation on radical prostatectomy specimens correlates with shorter bRFS independent of other prognostic parameters. 5-(10-) year bRFS rates for TRIM24 negative, low, medium and high expressing tumors are 93.1(93.1)%, 75.4(68.5)%, 54.9(47.5)% and 43.1(32.3)%, respectively. Of interest, tumors diagnosed as indolent disease, TRIM24 expression stratifies patients into specific risk groups. Increased TRIM24 expression associates with higher grade group, positive nodal status and extraprostatic tumor growth. TRIM24 assessment on prostate needle biopsies taken prior to treatment decision at time of initial diagnosis significantly correlates with recurrence after surgery. CONCLUSION: Using 2 large independent radical prostatectomy specimen cohorts, we found that TRIM24 expression predicts patients' risk to develop disease recurrence with high accuracy and independent from other established biomarkers. Further, this is the first study exploring TRIM24 expression on prostate needle biopsies which represents the clinically relevant tissue type on which biomarkers guide treatment decisions. Thus, we strongly suggest introducing TRIM24 evaluation in prostate needle biopsies in clinical routine as an inexpensive and simple immunohistochemical test.
Authors: Luise Klapper; Christian Idel; Patrick Kuppler; Tobias Jagomast; Amelie von Bernuth; Karl-Ludwig Bruchhage; Dirk Rades; Anne Offermann; Jutta Kirfel; Sven Perner; Julika Ribbat-Idel Journal: J Pers Med Date: 2022-06-17