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Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 7, pp 1751–1759 | Cite as

Combined loss of TFF3 and PTEN is associated with lethal outcome and overall survival in men with prostate cancer

  • Hatem Abou-Ouf
  • Sunita Ghosh
  • Adrian Box
  • Nallasivam Palanisamy
  • Tarek A. BismarEmail author
Original Article – Cancer Research

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.

Keywords

TFF3 PTEN Protein expression Immunohistochemistry Gleason score Androgen deprivation therapy Cancer specific mortality Biochemical recurrence 

Notes

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.

Compliance with ethical standards

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.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

432_2019_2933_MOESM1_ESM.tiff (213 kb)
Supplementary file1 (TIFF 213 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of Calgary Cumming School of Medicine and Calgary Laboratory ServicesCalgaryCanada
  2. 2.Department of Medical Oncology, Faculty of Medicine and DentistryUniversity of AlbertaEdmontonCanada
  3. 3.Department of UrologyVattikuti Urology Institute, Henry Ford Health System DetroitDetroitUSA
  4. 4.Department of OncologyUniversity of Calgary Cumming School of MedicineCalgaryCanada
  5. 5.Department of Biochemistry and Molecular BiologyUniversity of Calgary Cumming School of MedicineCalgaryCanada
  6. 6.Arnie Charbonneau Cancer Institute and Tom Baker Cancer CenterCalgaryCanada

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