Abstract
Background
Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease.
Design
228 radical prostatectomies (RP) and 318 transurethral resection of prostate (TURP) samples were assessed by immunohistochemistry (IHC) for TFF3 and by IHC and fluorescent in situ hybridization (FISH) for PTEN. Results of biomarkers expression were correlated with various pathological and clinical outcome parameters including biochemical recurrence (BCR) in the RP cohort and cancer-specific mortality (PCSM) and overall survival (OS) in the TURP cohort.
Results
TFF3 expression was detected in 131/226 (57.9%) RP samples and 148/318 (46.5%) of TURP cases. In general, TFF3 positivity was less frequently observed with advanced Gleason Groups. TFF3 expression was also assessed in relation to PTEN expression. Only 15–16% of TFF3-expressed cases were present in association with complete loss of PTEN expression in the TURP and localized cohorts, respectively. Loss of TFF3 expression was not related to BCR after RP, but was prognostic in the non-surgical cohort and associated with decrease OS and PCSM (HR 2.31, CI: 1.67–3.18, p < 0.0001) and (HR 3.99, CI: 2.43–6.56; p < 0.0001), respectively. Adjusting for Gleason score, combined loss of TFF3/PTEN was most associated with OS (HR 2.33, CI: 1.49–3.62; p < 0.0001) and PCSM (HR = 3.44, CI: 1.75–6.78, p < 0.0001).
Conclusion
The study documents for the first time significant association for combined status of TFF3 expression and PTEN loss in OS and PCSM in patients not managed by surgical intervention. Prospective assessment of PTEN and TFF3 may provide further insight into molecularly subtyping PCa and aid in stratifying patients at risk for lethal disease.
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Acknowledgements
The study was supported in part by the Prostate Cancer Foundation Young Investigator Award (T.A.B). This work is also supported by Prostate cancer Canada and is proudly funded by the Movember Foundation-Grant#B2013-01 and Funds from Ride for Dads (TAB). The authors would like to thank Mrs. Ruby Reyes for technical support in this manuscript.
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The study was approved by the U Calgary Cumming School of Medicine ethics review board and in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Abou-Ouf, H., Ghosh, S., Box, A. et al. Combined loss of TFF3 and PTEN is associated with lethal outcome and overall survival in men with prostate cancer. J Cancer Res Clin Oncol 145, 1751–1759 (2019). https://doi.org/10.1007/s00432-019-02933-z
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DOI: https://doi.org/10.1007/s00432-019-02933-z