The importance of protein kinase A in prostate cancer

Relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02

Alan Pollack, Kyounghwa Bae, Li Yan Khor, Tahseen Al-Saleem, M. Elizabeth Hammond, Varagur Venkatesan, Roger W. Byhardt, Sucha O. Asbell, William U. Shipley, Howard M. Sandler

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Wepreviously reported that protein kinase A type I (PKA RIα) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy (RT) ± short-term androgen deprivation (STAD) on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Here, we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKA RIα overexpression. Experimental Design: There were 313 cases in the RTOG 92-02 study cohort with available tissue and suitable staining by immunohistochemistry. Median follow-up was 10.1 years. The intensity of PKA RIα staining intensity was quantified manually and by image analysis. Multivariate analyseswere done for overallmortality using Cox proportional hazards models and for local failure, biochemical failure, distant metastasis, and cause-specific mortality using Fine and Gray's regression models. Results: The expression levels of PKA RIα, determined bymanual and image analysis, were strongly correlated (P < 0.0001). In the multivariate analyses, manual-quantified and image analysis-quantified PKA RIα staining intensities were independent predictors of distant metastasis (P < 0.01), local failure (P < 0.05), and biochemical failure (P ≤ 0.01). Furthermore, the benefit of long-term AD over STAD was much less when PKA RIα expression was high. Conclusions: PKA RIα overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD+ RT. In this series of contemporary high-risk patients, PKA RIα overexpression was associated with diminished response to LTAD + RT relative to STAD + RT, suggesting that such patients would be ideal for a PKA RIα knockdown strategy.

Original languageEnglish
Pages (from-to)5478-5484
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number17
DOIs
StatePublished - Sep 1 2009

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Radiation Oncology
Cyclic AMP-Dependent Protein Kinases
Prostatic Neoplasms
Radiotherapy
Androgens
Staining and Labeling
Neoplasm Metastasis
Proportional Hazards Models
Cohort Studies
Research Design
Multivariate Analysis
Immunohistochemistry
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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The importance of protein kinase A in prostate cancer : Relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02. / Pollack, Alan; Bae, Kyounghwa; Khor, Li Yan; Al-Saleem, Tahseen; Hammond, M. Elizabeth; Venkatesan, Varagur; Byhardt, Roger W.; Asbell, Sucha O.; Shipley, William U.; Sandler, Howard M.

In: Clinical Cancer Research, Vol. 15, No. 17, 01.09.2009, p. 5478-5484.

Research output: Contribution to journalArticle

Pollack, A, Bae, K, Khor, LY, Al-Saleem, T, Hammond, ME, Venkatesan, V, Byhardt, RW, Asbell, SO, Shipley, WU & Sandler, HM 2009, 'The importance of protein kinase A in prostate cancer: Relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02', Clinical Cancer Research, vol. 15, no. 17, pp. 5478-5484. https://doi.org/10.1158/1078-0432.CCR-08-2704
Pollack, Alan ; Bae, Kyounghwa ; Khor, Li Yan ; Al-Saleem, Tahseen ; Hammond, M. Elizabeth ; Venkatesan, Varagur ; Byhardt, Roger W. ; Asbell, Sucha O. ; Shipley, William U. ; Sandler, Howard M. / The importance of protein kinase A in prostate cancer : Relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 17. pp. 5478-5484.
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abstract = "Purpose: Wepreviously reported that protein kinase A type I (PKA RIα) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy (RT) ± short-term androgen deprivation (STAD) on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Here, we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKA RIα overexpression. Experimental Design: There were 313 cases in the RTOG 92-02 study cohort with available tissue and suitable staining by immunohistochemistry. Median follow-up was 10.1 years. The intensity of PKA RIα staining intensity was quantified manually and by image analysis. Multivariate analyseswere done for overallmortality using Cox proportional hazards models and for local failure, biochemical failure, distant metastasis, and cause-specific mortality using Fine and Gray's regression models. Results: The expression levels of PKA RIα, determined bymanual and image analysis, were strongly correlated (P < 0.0001). In the multivariate analyses, manual-quantified and image analysis-quantified PKA RIα staining intensities were independent predictors of distant metastasis (P < 0.01), local failure (P < 0.05), and biochemical failure (P ≤ 0.01). Furthermore, the benefit of long-term AD over STAD was much less when PKA RIα expression was high. Conclusions: PKA RIα overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD+ RT. In this series of contemporary high-risk patients, PKA RIα overexpression was associated with diminished response to LTAD + RT relative to STAD + RT, suggesting that such patients would be ideal for a PKA RIα knockdown strategy.",
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T2 - Relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02

AU - Pollack, Alan

AU - Bae, Kyounghwa

AU - Khor, Li Yan

AU - Al-Saleem, Tahseen

AU - Hammond, M. Elizabeth

AU - Venkatesan, Varagur

AU - Byhardt, Roger W.

AU - Asbell, Sucha O.

AU - Shipley, William U.

AU - Sandler, Howard M.

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N2 - Purpose: Wepreviously reported that protein kinase A type I (PKA RIα) overexpression was predictive of outcome in prostate cancer patients treated with radiotherapy (RT) ± short-term androgen deprivation (STAD) on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Here, we attempt to verify our prior findings and test the hypothesis that the relationship of the length of AD to patient outcome is affected by PKA RIα overexpression. Experimental Design: There were 313 cases in the RTOG 92-02 study cohort with available tissue and suitable staining by immunohistochemistry. Median follow-up was 10.1 years. The intensity of PKA RIα staining intensity was quantified manually and by image analysis. Multivariate analyseswere done for overallmortality using Cox proportional hazards models and for local failure, biochemical failure, distant metastasis, and cause-specific mortality using Fine and Gray's regression models. Results: The expression levels of PKA RIα, determined bymanual and image analysis, were strongly correlated (P < 0.0001). In the multivariate analyses, manual-quantified and image analysis-quantified PKA RIα staining intensities were independent predictors of distant metastasis (P < 0.01), local failure (P < 0.05), and biochemical failure (P ≤ 0.01). Furthermore, the benefit of long-term AD over STAD was much less when PKA RIα expression was high. Conclusions: PKA RIα overexpression has been shown in two RTOG trials to be associated with an increased risk of failure after AD+ RT. In this series of contemporary high-risk patients, PKA RIα overexpression was associated with diminished response to LTAD + RT relative to STAD + RT, suggesting that such patients would be ideal for a PKA RIα knockdown strategy.

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