Biomarker for aggressive prostate cancer identified

Overexpression of the protein MDM2 is “a strong and independent predictor” of prostate cancer metastasis and mortality, investigators with the Radiation Therapy Oncology Group (RTOG 92-02) announced at the annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) that is underway in Denver, Colorado.

“MDM2 is a feedback regulator of p53, both of which are involved in apoptosis in response to radiation and androgen derivation therapy,” principal investigator Dr. Alan Pollack of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, explained. In RTOG 92-02, immunohistochemical analysis was conducted in tissue samples from 469 men with prostate cancer. The researchers measured the expression of three biomarkers, MDM2, Ki-67 and p53, to determine their value as predictors of local failure, biochemical failure, distant metastasis and overall mortality.Dr. Pollack reported that MDM2 was a strong predictor of local failure, distant metastasis and overall mortality. Ki-67 was a strong predictor of distant metastasis. “When both factors are both high, that is a very strong predictor of metastatic disease,” Dr. Pollack said in an interview with Reuters Health.High MDM2 alone carried a 20.1% incidence of distant metastasis and 28.3% for overall mortality at 5 years. Low MDM2 was associated with an incidence of 11.5% for metastasis and 17.7% for overall mortality at five years. A high MDM2 and a high Ki-67 was associated with a 32.8% incidence of distant metastasis and 33.9% mortality at 5 years.The next step is to develop antisense MDM2 and thereby boost radiation and androgen deprivation therapy and lower metastasis and mortality rates. Dr. Pollack told Reuters Health that animal studies are currently underway.(Source: Reuters Health: Martha Kerr: Oncolink: October 2005.)