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Prostate Cancer

PTEN Protein Loss and Clinical Outcome from Castration-resistant Prostate Cancer Treated with Abiraterone Acetate

By: Roberta Ferraldeschia, Daniel Nava Rodriguesa, Ruth Riisnaesa, Susana Mirandaa, Ines Figueiredoa, Pasquale Rescignoa, Praful Ravia, Carmel Pezaroa, Aurelius Omlina, David Lorentea, Zafeiris Zafeirioua, Joaquin Mateoa, Amelia Altavillaa, Spyridon Siderisa, Diletta Bianchinia, Emily Grista, Khin Thwaya, Raquel Perez Lopeza, Nina Tunariua, Chris Parkerb, David Dearnaleyb, Alison Reida, Gerhardt Attarda and Johann de Bonoa

European Urology, Volume 67 Issue 4, April 2015, Pages 795-802

Published online: 01 April 2015

Keywords: Prostate cancer, PTEN, Abiraterone acetate, Immunohistochemistry

Abstract Full Text Full Text PDF (2,3 MB) Patient Summary

Abstract

Background

Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.

Objective

To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.

Design, setting, and participants

We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.

Outcome measurements and statistical analysis

The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.

Results and limitations

A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19–2.55; p = 0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12–2.28; p = 0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.

Conclusions

Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.

Patient summary

PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

Take Home Message

Loss of PTEN expression is associated with shorter median survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate.

Keywords: Prostate cancer, PTEN, Abiraterone acetate, Immunohistochemistry.

Footnotes

a Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK

b Academic Urology Unit, The Royal Marsden NHS Foundation Trust, London, UK

Corresponding author. Prostate Cancer Targeted Therapy Group, Royal Marsden NHS Foundation Trust, Cancer Therapeutics, The Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel. +44 2087224029.

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