Genes in Normal-Appearing Tissue May Predict PCa Recurrence

CHICAGO—Gene expression profiles, including the 17-gene Genomic Prostate Score (GPS), may be able to predict prostate cancer (PCa) aggressiveness when assessed in adjacent normal-appearing tissue, according to a new study presented at the 2013 American Society of Clinical Oncology annual meeting. 

The findings from this new study suggest the presence of an underlying field effect within the tumor-containing prostate gland.

“This really is a biologic observation that might lead to some interesting investigations down the road,” said investigator Eric A. Klein, MD, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic. “The implication is that there are early molecular changes in normal-appearing tissue that might be driving the biology of prostate cancer. … It is also possible that this sort of information can be used to decide who needs a rebiopsy.”

A high proportion of genes whose expression patterns predict PCa outcomes in tumors shows similar expression patterns in normal-appearing tissue, Dr. Klein noted. In addition, Dr. Klein and his team found that a majority of genes associated with outcomes in normal-appearing tissue are also predictive in tumor tissue and represent a wide range of biological pathways. The GPS, which was derived from tumor-based gene expression patterns, was associated with clinical recurrence when assessed in normal-appearing tissue. The strength of the association, however, was weaker in normal tissue than in the tumor. Components of the GPS that make the strongest contribution to the predictive ability in normal-appearing tissue were genes expressing stromal response and androgen signaling.

The 17-gene Oncotype DX Prostate Cancer Assay provides a 100-unit GPS. This assay has previously been independently validated to predict the likelihood of favorable pathology at the time of radical prostatectomy (RP) when performed on tumor tissue from needle biopsies. Dr. Klein and his colleagues conducted exploratory analyses to evaluate gene expression, including GPS, in adjacent normal-appearing tissue for prediction of clinical recurrence and PCa-related death.

The investigators looked at samplings from 127 patients with clinical recurrence and 374 without clinical recurrence. The 127 patients were part of a cohort of 2,641 patients treated with RP for T1/T2 prostate cancer. The researchers measured expression of 732 genes by qRT-PCR separately in the tumors and the adjacent normal-appearing tissue (defined as more than 3 mm from the tumor) specimens. A total of 410 evaluable patients had paired tumor and normal-appearing tissue.

Of the 405 genes that predicted outcome, 289 (71%) showed similar but weaker effects in the normal-appearing tissue. In addition, 47 genes were associated with clinical recurrence in the normal-appearing tissue. Among those 47 genes, 34 concordantly predicted clinical recurrence in the tumors.

GPS assessed in the normal-appearing tissue significantly predicted time to clinical recurrence. Each 20-unit increment in GPS was associated with an 80% increased likelihood of recurrence and a nearly twofold increased in PCa-related death. Stromal response genes were significantly predictive of prostate cancer death in the normal-appearing tissue.

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