| Molecular test combined with Gleason scoring identifies patients with the most aggressive prostate cancers Patients with the most aggressive prostate cancers can be identified with a combination of Gleason grading and molecular testing for cathepsin B and stefin proteins, according to an article in the June 15th issue of the journal Cancer. Most researchers evaluate tumors at least in part with use of the Gleason grading system, which assigns tumors a score between 2 and 10 with 10 representing the most undifferentiated cancers. Patients with a Gleason score from 7 to 10 have a higher risk of dying of prostate cancer than those with lower scores, but some patients with higher scores outlive some with lower scores. "This means that within any score, there are biologically aggressive and less aggressive forms of cancer," said Akhouri Sinha, lead investigator. "This makes it more difficult to predict outcomes for individual patients." In order to invade surrounding tissue and metastasize, malignant cells produce high levels of the enzyme cathepsin B, which destroys proteins in the surrounding connective tissue. Like normal cells, malignant cells also produce natural inhibitors called stefins. Akhouri Sinha, Donald Gleason, and colleagues hypothesized that prostate tumors in which levels of inhibitors were equal to or higher than cathepsin B would be less aggressive and those in which cathepsin B was higher would probably be more aggressive biologically. With use of prostate surgery samples from 97 prostate cancer patients and 8 patients with benign prostatic enlargement, the researchers measured the ratio of cathepsin B to the inhibitor stefin A. Malignant tissue came from Gleason grade 6 tumors, which appear relatively homogeneous under the microscope. The investigators found that the ratio of cathepsin B to stefin A was significantly higher in patients whose cancer had spread to one or more pelvic lymph nodes than in patients whose nodes were clear. "The ratio of cathepsin B to stefin A
reveals differences in tumors that are not visible under the microscope,"
said Sinha. "If this test were done on tumors of newly diagnosed
patients, we would have an indication of which cancers were most
aggressive, and we could give those patients aggressive treatment.
Those patients whose tumors show ratios of one, or less than one,
may require less aggressive treatment. This approach could also
be used for breast and colon cancer." |