Biomarker to predict prostate cancer prognosis

Researchers for the Mayo Clinic in the US have identified an immune molecule that appears to play a role in prostate cancer development and in predicting cancer recurrence and progression after surgery.

In a paper published this week in </>Cancer Research, the researchers demonstrate that nearly all normal, pre-malignant and cancerous prostate cells have B7-H3 on their surface.

The Mayo Clinic Cancer Center was the first to discover the B7-H family of immune molecules, proteins that normally help regulate the immune response process. They showed that B7-H3 and other members of the B7-H family, such as B7-H1, can have an inhibitory function and actually protect cancers as they develop.

B7-H3 was first identified as a new molecule in 2001, and since then multiple studies have been published pertaining to the role of B7-H1 in heralding a poor prognosis for patients with kidney cancer.

Although a number of hypotheses predicted that these molecules might enable cancer development, no one had shown it clinically prior to these studies.

Until now there were no strongly-predictive molecules for prostate cancer. The most notable other prostate biomarkers, prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA) are useful to diagnose prostate cancer. However, PSA tends to leave prostate cancer cells and migrate throughout the body, making it a poor target for therapy.

Unlike PSA, B7-H3 stays attached to the surface of prostate cancer cells and does not appear to migrate, thus making B7-H3 a particularly attractive target for therapy. The researchers believe that B7-H3 kills or paralyses immune cells that are trying to attack the cancer.

Their findings indicate that B7-H3 may prove useful as a diagnostic, prognostic and even therapeutic tool because it is stably or increasingly displayed by tumour cells as prostate cancers develop, even after initiation of anti-hormone therapy, which is the most common treatment for advanced prostate cancer.

"This discovery will allow physicians to individualise treatment and observation plans for prostate cancer patients," Dr Timothy Roth, a Mayo Clinic urology resident and lead author of the study, said. "Being able to tell a patient his specific risk after surgery, and perhaps even prior to surgery, will be a huge step forward."

The researchers examined tissue from 338 consecutive patients who had cancers confined to the prostate and were treated exclusively with a radical prostatectomy between 1995 and 1998.

All tumours and precancerous tissues displayed B7-H3, but patients with the highest levels of B7-H3 within their prostate tumours (19.8 per cent) were four times more likely to experience cancer progression compared to those with weak levels of B7-H3 within their tumours.

Moderate levels of B7-H3 also correlated with a slightly higher risk of recurrence (35 percent).

"Because B7-H3 is present in all prostate cancer tumours, and marked levels predict recurrence, we are able to forecast with much greater certainty the likelihood of cancer progression, regardless of therapeutic intervention," senior investigator Dr Eugene Kwon said.

For some patients, a 'watchful waiting' clinical approach is sometimes used to manage prostate cancer prior to resorting to therapy to see if the cancer becomes increasingly aggressive. The researchers say that the evaluation of B7-H3 levels in prostate biopsies from patients may soon help to determine which patients may benefit from a watchful waiting strategy versus early aggressive treatment.

To understand how B7-H3 affects the immune system, and whether a mutation of B7-H3 is involved in the anti-immune activity, more research is necessary. Mayo is planning clinical trials for a number of cancers in late 2008, and researchers are currently developing the necessary therapeutic antibodies to be used in these studies.

Investigators expect that clinical laboratory tests for the B7-H proteins may become available to assist with the assessment of patients with kidney cancer by late this year or early 2008, and then for prostate cancer patients shortly thereafter.

Source: Mayo Clinic