40421
document
MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer : RTOG 92-02 . PURPOSE MDM2 regulates p53 , which controls cell cycle arrest and apoptosis . Both proteins , along with Ki-67 , which is an established strong determinant of metastasis , have shown promise in predicting the outcome of men treated with radiation therapy ( RT ) with or without short-term androgen deprivation ( STAD ) . This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02 . PATIENTS AND METHODS Adequate tissue for immunohistochemistry was available for p53 , Ki-67 , and MDM2 analyses in 478 patient cases . The percentage of tumor nuclei staining positive ( PSP ) was quantified manually or by image analysis , and the per-sample mean intensity score ( MIS ) was quantified by image analysis . Cox regression models were used to estimate overall mortality ( OM ) , and Fine and Gray 's regressions were applied to the end points of distant metastasis ( DM ) and cause-specific mortality ( CSM ) . Results In multivariate analyses that adjusted for all markers and treatment covariates , MDM2 overexpression was significantly related to DM ( P = .02 ) and OM ( P = .003 ) , and Ki-67 overexpression was significantly related to DM ( P < .0001 ) , CSM ( P = .0007 ) , and OM ( P = .01 ) . P53 overexpression was significantly related to OM ( P = .02 ) . When considered in combination , the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points ( P < .001 for DM , CSM , and OM ) . CONCLUSION Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and , if validated , could be considered for risk stratification of patients with prostate cancer in clinical trials .
40422
Intervention_Physical
radiotherapy
40423
Intervention_Pharmacological
androgen deprivation
40424
Intervention_Physical
radiation therapy ( RT )
40425
Intervention_Pharmacological
short-term androgen deprivation ( STAD )
40426
Outcome_Physical
distant metastasis
40427
Outcome_Mortality
mortality
40428
Outcome_Physical
tumor nuclei staining positive
40429
Outcome_Other
per-sample mean intensity score
40430
Outcome_Physical
( MIS )
40431
Outcome_Mortality
overall mortality ( OM )
40432
Outcome_Physical
distant metastasis ( DM )
40433
Outcome_Mortality
cause-specific mortality ( CSM )
40434
Outcome_Physical
MDM2 overexpression
40435
Outcome_Physical
DM
40436
Outcome_Physical
DM
40437
Outcome_Mortality
CSM
40438
Outcome_Mortality
OM
40439
Outcome_Physical
P53 overexpression
40440
Outcome_Mortality
OM
40441
Outcome_Physical
overexpression of both Ki-67
40442
Outcome_Physical
MDM2
40443
Outcome_Other
significantly increased failure rates
40444
Outcome_Physical
MDM2
40445
Outcome_Physical
Ki-67 expression levels
40446
Outcome_Physical
distant metastasis
40447
Outcome_Mortality
mortality