Prostate Fusion Biopsy May Signal Disease Aggressiveness

For the first time, researchers say they have been able to use a prostate fusion biopsy to determine which tumors are the most aggressive. Researchers at the University of Michigan Comprehensive Cancer Center in Ann Arbor, Mich., conducted a pilot study on nine men undergoing active surveillance (Gleason score = 6) for prostate cancer. Using prostate fusion biopsies, they found that low-grade cancers may acquire genetic alterations that lead to aggressive cancer.¹

Each prostate cancer site was electronically tracked and 1 year later, additional tissue was obtained from the same intraprostatic site. The researchers found that five out of the nine men were reclassified on follow-up biopsy to a Gleason score ≥ 7. The team used ETS-related gene (ERG) immunohistochemistry (IHC) and targeted multiplexed PCR-based next generation sequencing (NGS) at each time point.

Study author Ganesh Palapattu, MD, who is chief of urologic oncology at the University of Michigan, said these new technologies are really refining the ability to diagnose and risk-stratify prostate cancer. As part of this investigation, DNA was co-isolated from 6-7 x 4μm formalin fixed paraffin embedded (FFPE) sections/sample.   

The analysis included 18 paired samples from nine patients. The study demonstrated that seven pairs (early/late) were evaluable for ERG IHC, and all the paired specimens uniformly were ERG+ (4 pairs) or ERG- (3 pairs). In addition, the researchers identified three prioritized driving somatic mutations across the cohort (SPOP F133L, BRCA2 K2524fs, and KMT2B Q2076X).

The researchers believe these are the first data that suggest that prostate cancers with a Gleason score ≥ 7 may arise clonally from Gleason score 6 cancers through acquired genetic alterations. Dr. Palapattu reported at the 2015 American Society of Clinical Oncology annual meeting (abstract 5017) that a targeted prostate biopsy could allow for repeat sampling of a clonal focus, and comprehensive molecular profiling of minute FFPE samples.²

Next, the research team will analyze biopsies from additional patients, but they say that if the association holds, it could suggest a panel test for low-grade prostate cancers to determine which patients might need more aggressive surveillance or perhaps even treatment upon initial diagnosis with a Gleason score of 6.

References:

• University of Michigan Comprehensive Cancer Center. (2015). U-M researchers highlight work on colorectal cancer, sarcoma, prostate cancer and oral chemotherapy.
• Palapattu GS, Cani AK, Huang J, et al. (2015). Progression of low- to high-grade prostate cancer: Molecular profiling of tissue obtained by serial targeted biopsy.  Journal of Clinical Oncology, 33(15).