Increased expression of the PTOV1 gene correlates with higher risk for progression of high-grade prostatic intraepithelial neoplasia to prostate cancer and decreased expression correlates with lower risk, according to an article in the May 1 issue of Clinical Cancer Research.

Currently, these patients are advised to undergo repeated needle biopsies as a precaution.

"This is the first high-grade prostatic intraepithelial neoplasia biomarker to be associated with prostate cancer development," said the study's lead author, Rosanna Paciucci, PhD, a researcher at the Vall d´Hebron Hospital Research Institute in Barcelona.

She said that when the results are validated, the PTOV1 gene marker could be used to determine which men with high-grade prostatic intraepithelial neoplasia are at substantial risk of developing prostate cancer.

"Those patients with a high PTOV1 score should undergo an immediate repeat biopsy," Paciucci said. In addition, men who test low for PTOVI may not need to receive future "annoying and useless" biopsies, she said. "We estimate that we can save 40 percent of unnecessary biopsies - those that are repetitively negative and contain high-grade prostatic intraepithelial neoplasia lesions that do not develop into cancer."

While the researchers do not know the precise biochemical function of PTOV1, they say they have found this protein promotes proliferation of cancer cells when it is over-expressed, as occurs in prostate cancer cells.

high-grade prostatic intraepithelial neoplasia is defined as a pre-malignant lesion present in most cancerous prostates. Because high-grade prostatic intraepithelial neoplasia lesions are also associated with the presence of cancer in many patients, men whose biopsies have one or more lesions are often re-biopsied until cancer is detected, Paciucci said.

In most recent studies, the average risk of cancer following a diagnosis of isolated high-grade prostatic intraepithelial neoplasia in biopsy ranged from 20 to 30 percent, the researchers said. Although other researchers have found markers in the lesions, none have been able to discriminate between lesions that will progress to cancer, according to the research team.

In the current study, the research team analyzed lesions from 140 patients: the positive control group comprised 79 patients diagnosed with prostate cancer who had their prostate glands surgically removed and who had been earlier diagnosed with high-grade prostatic intraepithelial neoplasia, the negative control group included 11 patients with bladder cancer who had both their diseased bladder and healthy prostate removed, and the study group comprised 50 patients diagnosed with high-grade prostatic intraepithelial neoplasia but not prostate cancer. The study group had an average of 2.5 biopsies each between 2000 and 2004.

Finding that PTOV1 gene expression was elevated in lesions associated with cancer, the investigators used tissue microarray and immunohistochemical analyses to see whether PTOV1 protein levels could discriminate pre-malignant lesions that did not develop into prostate cancer.

They considered both the number of cells that express the protein and the intensity of the expression, and derived a quantitative score (Hscore) that ranged from 0 to 300. From this, they calculated that an Hscore of 100 represented a highly sensitive malignancy threshold. "This means that when PTOV1 Hscore is equal or above 100 the possibility to find cancer in the subsequent biopsy is 90 percent," Paciucci said. "Currently, the diagnosis of cancer is made only when the cancer lesion is seen in the biopsy."

By adding analysis of PTOV1, the positive predictive value (the chance that the lesion will become cancerous) of all samples, including those with a score of less than 100, is 34 percent, and the negative predictive value (the chance that the lesion will not become cancerous) is more than 95 percent, Paciucci added.

Paciucci cautioned that the study results need to be confirmed among a larger study group. "From this validation we can expect to improve the current rate of early detection of cancer," she said.