MDM2 as a predictor of prostate carcinoma outcome

An analysis of radiation therapy oncology group protocol 8610

Li Yan Khor, Michelle DeSilvio, Tahseen Al-Saleem, M. Elizabeth Hammond, David Grignon, William Sause, Michael Pilepich, Paul Okunieff, Howard Sandler, Alan Pollack

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

BACKGROUND. The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation. METHODS. Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5% nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity. RESULTS. Overexpression of MDM2 by manual counts was seen in 44% (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, ≤ 3% versus > 3%, was related to 5-year DM rates in univariate analyses (32.6% vs. 45.8%; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant. CONCLUSIONS. MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate.

Original languageEnglish (US)
Pages (from-to)962-967
Number of pages6
JournalCancer
Volume104
Issue number5
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

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Radiation Oncology
Prostate
Radiotherapy
Staining and Labeling
Carcinoma
Neoplasm Metastasis
Multivariate Analysis
Tumor Suppressor Protein p53
Mortality
Ubiquitin
Cell Cycle Checkpoints
Androgens
Cohort Studies
Apoptosis
Neoplasms

Keywords

  • Androgen deprivation
  • Distant metastasis
  • MDM2
  • Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Khor, L. Y., DeSilvio, M., Al-Saleem, T., Hammond, M. E., Grignon, D., Sause, W., ... Pollack, A. (2005). MDM2 as a predictor of prostate carcinoma outcome: An analysis of radiation therapy oncology group protocol 8610. Cancer, 104(5), 962-967. https://doi.org/10.1002/cncr.21261

MDM2 as a predictor of prostate carcinoma outcome : An analysis of radiation therapy oncology group protocol 8610. / Khor, Li Yan; DeSilvio, Michelle; Al-Saleem, Tahseen; Hammond, M. Elizabeth; Grignon, David; Sause, William; Pilepich, Michael; Okunieff, Paul; Sandler, Howard; Pollack, Alan.

In: Cancer, Vol. 104, No. 5, 01.09.2005, p. 962-967.

Research output: Contribution to journalArticle

Khor, LY, DeSilvio, M, Al-Saleem, T, Hammond, ME, Grignon, D, Sause, W, Pilepich, M, Okunieff, P, Sandler, H & Pollack, A 2005, 'MDM2 as a predictor of prostate carcinoma outcome: An analysis of radiation therapy oncology group protocol 8610', Cancer, vol. 104, no. 5, pp. 962-967. https://doi.org/10.1002/cncr.21261
Khor, Li Yan ; DeSilvio, Michelle ; Al-Saleem, Tahseen ; Hammond, M. Elizabeth ; Grignon, David ; Sause, William ; Pilepich, Michael ; Okunieff, Paul ; Sandler, Howard ; Pollack, Alan. / MDM2 as a predictor of prostate carcinoma outcome : An analysis of radiation therapy oncology group protocol 8610. In: Cancer. 2005 ; Vol. 104, No. 5. pp. 962-967.
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abstract = "BACKGROUND. The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation. METHODS. Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5{\%} nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity. RESULTS. Overexpression of MDM2 by manual counts was seen in 44{\%} (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, ≤ 3{\%} versus > 3{\%}, was related to 5-year DM rates in univariate analyses (32.6{\%} vs. 45.8{\%}; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant. CONCLUSIONS. MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate.",
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T2 - An analysis of radiation therapy oncology group protocol 8610

AU - Khor, Li Yan

AU - DeSilvio, Michelle

AU - Al-Saleem, Tahseen

AU - Hammond, M. Elizabeth

AU - Grignon, David

AU - Sause, William

AU - Pilepich, Michael

AU - Okunieff, Paul

AU - Sandler, Howard

AU - Pollack, Alan

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N2 - BACKGROUND. The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation. METHODS. Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5% nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity. RESULTS. Overexpression of MDM2 by manual counts was seen in 44% (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, ≤ 3% versus > 3%, was related to 5-year DM rates in univariate analyses (32.6% vs. 45.8%; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant. CONCLUSIONS. MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate.

AB - BACKGROUND. The MDM2 oncoprotein promotes p53 degradation via ubiquitin, establishing negative feedback control of p53 and consequently affecting cell cycle arrest and apoptosis. The authors evaluated the association between MDM2 expression and local failure, distant metastasis (DM), cause-specific mortality, and overall mortality in men treated in Radiation Therapy Oncology Group 8610 with radiotherapy, with or without androgen deprivation. METHODS. Of the 456 eligible and analyzable patients (parent cohort), adequate archival diagnostic tissue specimens from 108 patients were available for MDM2 analysis (MDM2 cohort). Cox proportional hazards multivariate analysis (MVA) was used to determine the relation of MDM2 to the endpoints. MDM2 overexpression was manually classified as > 5% nuclear staining. An image analysis system was also used to quantify the proportion of tumor nuclei with MDM2 staining (ACIS index) and staining intensity. RESULTS. Overexpression of MDM2 by manual counts was seen in 44% (n = 47) of the patients. In the manual count analysis, there was no significant relation between MDM2 overexpression and outcome. The ACIS index, using a cutoff point defined by the median value, ≤ 3% versus > 3%, was related to 5-year DM rates in univariate analyses (32.6% vs. 45.8%; P = 0.057) and MVA (P = 0.06). The intensity of MDM2 staining was not significant. CONCLUSIONS. MDM2 expression quantified by image analysis was weakly associated with DM. The cohort examined was relatively small and with larger patient numbers, MDM2 overexpression may emerge as a more significant covariate.

KW - Androgen deprivation

KW - Distant metastasis

KW - MDM2

KW - Radiotherapy

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