Biomarker can predict aggressive prostate cancer

When a man is diagnosed with prostate cancer, a host of tools can be used to determine the type and extent of his disease. These tools include a basic PSA blood test, digital rectal exam, tissue biopsy, and a Gleason Score – a mathematical score based on tissue analysis that predicts whether the cancer is aggressive or not and helps doctors choose the most appropriate treatment.

The lowest Gleason score of 6 is assigned to cancers that are least likely to be aggressive.

Scores 8 to 10 are reserved for cancers more likely to grow and spread.

A score of 7 is attached to intermediate-grade tumors whose growth and spread is predicted to be moderate, in between the other two. But Gleason 7 cancers can be tricky, because not all Gleason 7 cancers are alike.

Some Gleason 7 cancers are aggressive and suggest a patient’s cancer, when diagnosed, may have already advanced. Other Gleason 7 cancers, 75 percent to be exact, are the less aggressive type. But identifying aggressive and nonaggressive types has traditionally been challenging, and some men diagnosed with the more aggressive type were later found to have the less aggressive disease.

But now, researchers at MD Anderson have identified a biomarker that can predict which prostate cancer patients with a Gleason score of 7 will have the more aggressive form of cancer.

Their results are reported in the journal Clinical Cancer Research, a publication of the American Association of Cancer Research.

The biomarker that predicts aggressive Gleason 7 prostate cancer is located next to the KLK3 gene – a gene on chromosome 19. The KLK3 gene produces prostate-specific antigen, or PSA, an important tumor maker used in the diagnosis and monitoring of prostate cancer. Elevated PSA levels can signal the presence of cancer.

In addition, the researchers found that a single nucleotide polymorphism – the most common type of genetic variation among people -- on the KLK3 gene is more apparent in patients with a Gleason score of 7, which further advances knowledge of Gleason 7 prostate cancer.

“This is the first report that I am aware of that indicates a genetic variant can stratify Gleason 7 prostate cancer patients,” said Jian Gu, Ph.D., associate professor at MD Anderson and a key investigator on the study.

Treatment options for patients with a Gleason score of 7 are controversial. Treatment targeting the aggressive form of the cancer meant over-treating patients with the less aggressive form.

“It is critical that we develop personalized treatments based on additional biomarkers to stratify Gleason score 7 prostate cancers,” said Xifeng Wu, M.D., Ph.D., professor and chair of Epidemiology and the study’s lead investigator.

Wu and her team are expanding their initial study and working to identify even more genetic variants and biomarkers for the prognosis of prostate cancer patients.