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PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate

Ferraldeschi, Roberta, Nava Rodrigues, Daniel, Riisnaes, Ruth, Miranda, Susana, Figueiredo, Ines, Rescigno, Pasquale, Ravi, Praful, Pezaro, Carmel, Omlin, Aurelius, Lorente, David, Zafeiriou, Zafeiris, Mateo, Joaquin, Altavilla, Amelia, Sideris, Spyridon, Bianchini, Diletta, Grist, Emily, Thway, Khin, Perez Lopez, Raquel, Tunariu, Nina, Parker, Chris, Dearnaley, David, Reid, Alison, Attard, Gerhardt and de Bono, Johann 2015, PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate, European urology, vol. 67, no. 4, pp. 795-802, doi: 10.1016/j.eururo.2014.10.027.

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Title PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate
Author(s) Ferraldeschi, Roberta
Nava Rodrigues, Daniel
Riisnaes, Ruth
Miranda, Susana
Figueiredo, Ines
Rescigno, Pasquale
Ravi, Praful
Pezaro, Carmel
Omlin, Aurelius
Lorente, David
Zafeiriou, Zafeiris
Mateo, Joaquin
Altavilla, Amelia
Sideris, Spyridon
Bianchini, Diletta
Grist, Emily
Thway, Khin
Perez Lopez, Raquel
Tunariu, Nina
Parker, Chris
Dearnaley, David
Reid, Alison
Attard, Gerhardt
de Bono, Johann
Journal name European urology
Volume number 67
Issue number 4
Start page 795
End page 802
Total pages 8
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2015-04
ISSN 1873-7560
Keyword(s) Abiraterone acetate
Immunohistochemistry
PTEN
Prostate cancer
Summary 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.
Language eng
DOI 10.1016/j.eururo.2014.10.027
Field of Research 1103 Clinical Sciences
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30081342

Document type: Journal Article
Collection: School of Medicine
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