Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer

Michael G. Heckman, Alexander S. Parker, Kevin J. Wu, Tracy W. Hilton, Stephen J. Ko, Thomas M. Pisansky, Steven E. Schild, Li Yan Khor, Elizabeth H. Hammond, Alan Pollack, Steven J. Buskirk

Research output: Contribution to journalArticle

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Abstract

Background. AND PURPOSE The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer. Material And Methods. We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Results. Compared to patients with low staining (âmedian) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95% CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95% CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95% CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining. CONCLUSIONS Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.

Original languageEnglish
Pages (from-to)1757-1766
Number of pages10
JournalProstate
Volume72
Issue number16
DOIs
StatePublished - Dec 1 2012

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Salvage Therapy
Prostatic Neoplasms
Radiotherapy
Biomarkers
Staining and Labeling
Recurrence
Confidence Intervals
Prostatectomy
Tumor Biomarkers
Proportional Hazards Models
Monoclonal Antibodies

Keywords

  • biochemical recurrence
  • prostate cancer
  • salvage radiation therapy
  • tumor biomarker

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Heckman, M. G., Parker, A. S., Wu, K. J., Hilton, T. W., Ko, S. J., Pisansky, T. M., ... Buskirk, S. J. (2012). Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer. Prostate, 72(16), 1757-1766. https://doi.org/10.1002/pros.22528

Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer. / Heckman, Michael G.; Parker, Alexander S.; Wu, Kevin J.; Hilton, Tracy W.; Ko, Stephen J.; Pisansky, Thomas M.; Schild, Steven E.; Khor, Li Yan; Hammond, Elizabeth H.; Pollack, Alan; Buskirk, Steven J.

In: Prostate, Vol. 72, No. 16, 01.12.2012, p. 1757-1766.

Research output: Contribution to journalArticle

Heckman, MG, Parker, AS, Wu, KJ, Hilton, TW, Ko, SJ, Pisansky, TM, Schild, SE, Khor, LY, Hammond, EH, Pollack, A & Buskirk, SJ 2012, 'Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer', Prostate, vol. 72, no. 16, pp. 1757-1766. https://doi.org/10.1002/pros.22528
Heckman, Michael G. ; Parker, Alexander S. ; Wu, Kevin J. ; Hilton, Tracy W. ; Ko, Stephen J. ; Pisansky, Thomas M. ; Schild, Steven E. ; Khor, Li Yan ; Hammond, Elizabeth H. ; Pollack, Alan ; Buskirk, Steven J. / Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer. In: Prostate. 2012 ; Vol. 72, No. 16. pp. 1757-1766.
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abstract = "Background. AND PURPOSE The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer. Material And Methods. We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95{\%} confidence intervals (CIs) were estimated. Results. Compared to patients with low staining ({\^a}median) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95{\%} CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95{\%} CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95{\%} CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining. CONCLUSIONS Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.",
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T1 - Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer

AU - Heckman, Michael G.

AU - Parker, Alexander S.

AU - Wu, Kevin J.

AU - Hilton, Tracy W.

AU - Ko, Stephen J.

AU - Pisansky, Thomas M.

AU - Schild, Steven E.

AU - Khor, Li Yan

AU - Hammond, Elizabeth H.

AU - Pollack, Alan

AU - Buskirk, Steven J.

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N2 - Background. AND PURPOSE The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer. Material And Methods. We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Results. Compared to patients with low staining (âmedian) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95% CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95% CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95% CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining. CONCLUSIONS Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.

AB - Background. AND PURPOSE The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer. Material And Methods. We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Results. Compared to patients with low staining (âmedian) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95% CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95% CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95% CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining. CONCLUSIONS Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.

KW - biochemical recurrence

KW - prostate cancer

KW - salvage radiation therapy

KW - tumor biomarker

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