Study identifies four genes tied to prostate cancer

A recent study has pinpointed four genes linked to prostate cancer, a finding that researchers say could significantly improve diagnosis and treatment by identifying slow-growing cancers that do not need to be treated and by developing targeted therapies for aggressive forms of the disease.

One of the four genes, HEY2, shows particular promise as an indicator of aggressive prostate cancer.

"As with breast cancer, everybody wants to find the holy grail-the indicator of how the cancer will behave in the future and what treatment, if any, is warranted," said senior author Sharon Mair, MD, of Sharp Grossmont Hospital, La Mesa, CA. "I spoke to many prostate cancer patients who said they wish they’d never had treatment because they were left incontinent, impotent, or both."

In the study, which was published in the American Journal of Clinical Pathology (2012; 137:918-30), the authors analyzed biopsy specimens of 240 patients who had been diagnosed with prostate cancer and underwent radical prostatectomy, and then followed their progress. The group analyzed antibodies to the protein products of 20 genes in both benign and malignant cells from each patient and then compared their findings with patient outcomes. Four genetic markers were clearly associated with prostate cancer prognosis-two of which were associated with slow-growing cancer and two with aggressive cancer-and all 240 patients tested positive to one or more antibodies to the four.

Of the 240 patients, 156 (65%) remained disease-free throughout the duration of their follow-up (from 5 years to 11 years and 10 months, after surgery) and were more likely to test positive for the slow-growing genetic markers and less likely to test positive for the aggressive genetic markers. In 84 of the men (35%), the disease progressed to biochemical failure, local tumor recurrence, or metastasis, beyond the pelvis.

Fifteen of the men had only biochemical failure, 45 had additional local recurrence, and 24 had additional distant metastasis, although none of the patients in the study died from prostate cancer during the study follow-up period. Patients in the additional distant metastasis group were more likely to test positive for STMN1 and HEY2, and 32% of patients whose cancer spread distantly tested positive for HEY2.

"If these results are confirmed, we believe a simple kit could be developed to test all four antibodies to those genes," said Omar Hameed, MD, of the American Society for Clinical Pathology and Vanderbilt University Medical Center, Nashville, TN, who was not involved with the study. "This would provide the doctor with a risk assessment tool that could be used to help determine which patients should receive radical treatment and those who can be safely watched with regular PSA tests."

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