PTEN Status Predicts Prostate Cancer Outcomes As Well As Multigene Panel

By Will Boggs MD

NEW YORK (Reuters Health) - PTEN loss by tumor immunohistochemistry (IHC) predicts prostate-cancer outcomes after radical prostatectomy as well as a commercial multigene panel does.

The expression status of several genes involved in prostate-cancer pathogenesis has been shown to improve risk stratification relative to conventional clinical variables. There have been few comparative studies between the two clinical approaches employed to assess genetic features of prostate-cancer tissue (commercial gene panel assays of tumor RNA and IHC staining of tumor tissue).

Dr. Michael S. Leapman from Yale University School of Medicine, in New Haven, Connecticut, and colleagues compared the prognostic utility of a commercially-based gene expression test examining a panel of cell-cycle progression (CCP) genes versus the IHC expression status of three markers of genomic alterations in prostate cancer (PTEN, ERG, and Ki-67).

They studied 424 men with clinically localized prostate cancer who were treated with radical prostatectomy.

The median CCP score was -0.33, and IHC demonstrated PTEN loss in 19% of patients, high Ki-67 expression in 52% and positive ERG expression in 42% (with 5% demonstrating all three), the team reports in European Urology, online September 1.

PTEN loss was associated with a 5.20-fold increased risk of metastasis/prostate-cancer-specific mortality (PCSM), whereas Ki-67 overexpression and ERG positivity were not significantly associated with this primary outcome.

The CCP score was significantly associated with both biochemical recurrence and metastasis/PCSM.

After adjustment for the Cancer of the Prostate Risk Assessment score (CAPRA-S), PTEN loss and CCP score remained independently associated with metastasis/PCSM.

The c-index for predicting the risk of metastasis/PCSM was virtually the same for the model consisting of PTEN status and CAPRA-S (0.80) and the model with CCP and CAPRA-S (0.81).

"These findings indicate that integrating PTEN status alone with clinical information would serve as a potentially valuable approach to improve risk assessment with relatively minor financial cost or need for external processing," the researchers conclude.

Dr. Eric A. Klein from Cleveland Clinic, in Cleveland, Ohio, recently found that a 17-gene score could predict prostate cancer outcomes better than PTEN status. He told Reuters Health by email, "The article raises an important issue: new tests come along all the time as technology and new ways of measuring biological potential come along."

"I guess the conclusion is: it depends on which test is being looked at, and I would not generalize that all genomic tests are no better than IHC," said Dr. Klein, who was not involved in the new study. "Clearly some are better, and decisions need to be made on a case-by-case basis for each test."

Dr. Leapman did not respond to a request for comments.


Eur Urol 2018.

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