PTEN expression and risk for progressive disease in low-risk patients

A new paper by Cuzick and colleagues has suggested that loss of expression of the PTEN gene, which encodes for a protein known as phosphatase and tensin homologue (PTEN), may be significantly associated with heightened risk of progressive disease in a cohort of nominally low-risk patients.

Cuzick et al. carried out a laboratory study of tissue samples (“chips”) from the prostates of a cohort of 675 men who had been diagnosed with low-risk prostate cancer as a consequence of a transurethral resection of the prostate (a TURP) as treatment for an enlarged prostate causing problems with urination. The patients were all managed conservatively after their initial diagnosis. (In other words, no further treatment was given until it was clear that such treatment was necessary.)

Cuzick and his colleagues used two different methods by which to measure the presence of PTEN in the “chips”: immunochemistry (IHC) and fluorescent in situ hybridization (FISH).

Here is what they found:

  • Loss of expression of the PTEN gene was observed in 18 percent of cases (when measured using IHC).
  • On univariate analysis, this loss of expression of the PTEN gene (when measured using IHC) was
    • Significantly associated with prostate cancer-specific mortality death (hazard ratio [HR] = 3.51)
    • Highly predictive of prostate cancer-specific mortality in the 50 percent of patients with a low risk score based on Gleason score, PSA, Ki-67, and extent of disease (HR = 7.4)
    • Of no prognostic value in higher-risk patients.
  • By comparison, loss of expression of the PTEN gene (when measured using the FISH assay) was
    • Only weakly associated with loss of expression of the PTEN gene (when measured using the IHC assay).
    • Predictive of death from prostate cancer in univariate but not on multivariate analysis.

Cuzick et al. conclude that “In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.”

It is a little unclear to what extent this information is of clinically practical value here in the USA today because:

  • The number of men who undergo TURP as a first-line treatment for benign prostatic hyperplasia (BPH) has declined significantly since the mid 1990s.
  • These data may only be applicable to men who have progressive disease after a finding of cancer on TURP.
  • Even though the loss of expression was highly predictive of prostate cancer-specific mortality in men with low-risk disease, there was clearly a significant “false positive” rate (i.e., men found to have lost expression of the PTEN gene who nevertheless did not go on to die from prostate cancer)

It seems to The “New” Prostate Cancer InfoLink that, although these data are technically and intellectually interesting, a good deal more study will be needed to know how best to apply data of this type in the diagnosis and management of patients. And that’s before one even tried to understand why the data are only significant when PTEN expression levels are being measured using immunohistochemical methods as opposed to FISH.

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