Another possible urine test for detection of prostate cancer?

A study just published in Clinical Cancer Research suggests that levels of a protein called engrailed-2 (EN2) in urine may be indicative of risk for prostate cancer.

According to the new article by Morgan et al., they carried out initial tests by measuring the levels of EN2 in the “first-pass” urine (prior to any digital rectal examination) of men with urinary symptoms referred to their clinic to exclude or confirm for the presence of prostate cancer and in a series of normal “controls.”

The results from this initial trial are as follows:

  • Tests were conducted on urine for 82 men known to have prostate cancer and on 102 controls.
  • The presence of EN2 was predictive of prostate cancer — with a sensitivity of 66 percent and a specificity of 88.2 percent.
  • There was no correlation between the presence of EN2 and the level of PSA.

The authors were able to confirm these initial results in tests independently conducted at a second academic center. They conclude only that urinary EN2 is a potential candidate biomarker of prostate cancer, and that a larger multi-center study will be necessary in order to better assess the diagnostic potential of EN2.

According to information from the Press Association in the UK, EN2 is a protein that is normally expressed during the development of human embryos, but is switched off at the time of a child’s birth. The researchers have been able to show that expression of EN2 is re-activated in a large percentage of men with prostate cancer.

Professor Hardev Pandha of the University of Surrey, the leader of the research team, is quoted as saying: “In this study we showed that the new test was twice as good at finding prostate cancer as the standard PSA test. Only rarely did we find EN2 in the urine of men who were cancer free so, if we find EN2 we can be reasonably sure that a man has prostate cancer.”

There would be great value in a simple urine test that is highly predictive of risk for prostate cancer — especially if data from such a test could be combined with PSA data to give a better ability to differentiate between risk levels for prostate cancer. However, The “New” Prostate Cancer InfoLink recognizes that potential tests like this have been identified before and gone nowhere, so we will need to wait and see whether further data confirm the initial promise of EN2.


6 Responses

  1. Professor Pandha is quoted as saying: “Only rarely did we find EN2 in the urine of men who were cancer free so, if we find EN2 we can be reasonably sure that a man has prostate cancer.”

    Well, I respectfully disagree.

    Not finding EN2 means, with a high degree of certitude — 88.2% — that the man doesn’t have prostate cancer. Finding EN2 in the urine is a much weaker indication — 66% — that he does have cancer. In other words, finding EN2 in the urine may indicate one has cancer (true positive) or may not (false negative).

    Given that the research showed, “There was no correlation between the presence of EN2 and the level of PSA.” I fail to understand how it can be used in conjunction with PSA testing.

  2. Dear Reuven: The reason that one might be able to use PSA and EN2 data together to increase the potential accuracy of the need for a biopsy is exactly because they are (apparently) measuring two very different risks for the presence of prostate cancer that are in no way dependent on each other.

    Furthermore, the finding of EN2 in the urine of a man who did not have a positive biopsy for prostate cancer can not be used to state that he didn’t have prostate cancer (yet). All that we can be sure of is that he did not have a diagnosis of prostate cancer on biopsy … but that occurs commonly, because the biopsy needles miss the cancer. It may well be that, in fact, the presence of EN2 is 100% accurate for the presence of prostate cancer — but that we aren’t always able to find the cancer on biopsy.

    All biological tests have “false” negatives and “false” positives — but one has to be careful to interpret why they appear to be “false.” Since a prostate biopsy is inherently a poor diagnostic tool itself, one needs to recognize that a negative biopsy is not necessarily an accurate indicator of the absence of prostate cancer.

  3. I am 29 years old and have difficult urinating.

    I had gonorrhea 2 months ago and was treated twice, differently, becoz the first treatment did not bear fruit. Could it be a sign of cancer and at this age?

  4. Dear John:

    Prostate cancer in a young man of 29 is extremely, extremely rare. It is very unlikely to be your problem. It seems much more likely that you simply have some type of complication associated with your prior infection, but you might want to talk to a specialist in urology.

  5. Is the EN2 stick test available in the US?

  6. The EN2 test isn’t commercially available anywhere, yet, as far as I am aware. It is still in development. It might or might not actually be proven to be accurate and effective in large clinical trials.

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