TMPRSS2-ERG and Prostate Cancer Outcomes
New study shows common prostate cancer mutation does not strongly predict disease recurrence or mortality among men treated with radical prostatectomy
July 6, 2012 -- About half of all diagnosed prostate cancers are not destined to become lethal forms of the disease. But because physicians are unable to predict with good accuracy which prostate cancers will remain indolent, slow growing and non life-threatening and which need immediate and aggressive treatment in order to prevent death, overtreatment of prostate cancer is a major concern. Researchers are desperately attempting to find biological markers of aggressive prostate cancers that will help doctors and men diagnosed with prostate cancer make better- informed treatment decisions.
A new study in Cancer Epidemiology, Biomarkers & Prevention that was partially funded by the Prostate Cancer Foundation has determined that a common genetic mutation found in prostate tumors holds little prognostic value in terms lethality of the tumor or whether prostate cancer will recur after surgery to remove the cancerous prostate.
The mutation evaluated in the study is a chromosomal re-arrangement that results in the erroneous fusion of two genes: TMPRSS2 and ERG. Since its discovery in 2005 by PCF-funded researchers Drs. Scott Tomlins, Arul Chinnaiyan and Mark Rubin, the TMPRSS2-ERG fusion has excited the question of whether or not prostate cancers that are TMPRSS2-ERG positive are associated with more deadly cancers—prior research has linked the fusions to poor outcomes, while other research found no association.
Now, the study in Cancer Epidemiology, Biomarkers & Prevention that followed a large cohort of men who underwent radical prostatectomy for the initial treatment of their cancers has produced a more definitive answer, finding no association of TMPRSS2-ERG with disease progression. In addition to the cohort study of 1,180 men who were followed for a median time of 12.6 years post surgery, the study performed a meta-analysis review of 47 additional studies, looking at 5,074 men over time for rates of disease recurrence and prostate-specific mortality. Again, being positive for the gene fusion was not linked to higher rates of disease recurrence after surgery or aggressive, lethal forms of the disease developing years later.
“The presence of this fusion in prostate tissue seems to act as a tipping point toward the development of cells becoming cancerous, but in and of itself, doesn’t weaponize those cells to their deadest forms that can no longer be contained with local treatments,” says Dr. Jonathan W. Simons, CEO of the Prostate Cancer Foundation. “For that to occur, other environmental or genetic events must occur that goad early cancer cells towards aggression.”
The senior author of the paper is PCF-funded Dr. Lorelei Mucci at the Harvard School of Public Health who says she and others are currently looking into the interplay of TMPRSS2-ERG fusion-positive cancers and environmental/lifestyle factors such as obesity in prostate cancer survival. (Obesity has been linked to worse outcomes in prostate cancer with higher rates of recurrence after surgery and aggressive disease reported in prior research.) This research should help shed light on whether the accumulation of additional molecular changes in combination with TMPRSS2-ERG fusion can push men whose tumors are positive for the fusion to more aggressive states of the disease.
An additional area of study will be to examine if the presence or absence of the fusion affects men’s response to certain drug treatments for prostate cancer such as androgen deprivation therapy that is used to starve tumors of hormones that fuel their growth.
“This is an interesting question and one that our group is interested in pursuing,” says Dr. Mucci.