Biomarker predicts malignancy potential of prostate lesions

Spanish researchers have found a means of distinguishing between high-grade prostatic intraepithelial neoplasia (HGPIN) lesions destined to become cancerous and those that will remain benign, which may spare patients the discomfort and inconvenience of unnecessary needle biopsies, according to a study in Clinical Cancer Research (2008; 14:2617-22).

The research team found that expression of the PTOV1 gene in HGPIN lesions is linked to prostate cancer development, and that the higher the expression, the more likely it is that subsequent biopsies will find cancer. The reverse is also true: lack of PTOV1 reduces the risk of prostate cancer.

“This is the first HGPIN biomarker to be associated with prostate cancer development,” said lead author Rosanna Paciucci, PhD, of the Vall d´Hebrón Hospital Research Institute in Barcelona. “Those patients with a high PTOV1 score should undergo an immediate repeat biopsy. On the flip side, men who test low for PTOV1 may not need to receive future biopsies. We estimate that we can save 40% of unnecessary biopsies-those that are repetitively negative and contain HGPIN lesions that do not develop into cancer.”

In the study, the team analyzed HGPIN 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 HGPIN; 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 HGPIN 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 HGPIN associated with cancer, the investigators used tissue microarray and immunohistochemical analyses to determine whether PTOV1 protein levels could discriminate these pre-malignant lesions from HGPIN 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.

“This means that when PTOV1 Hscore is equal or above 100 the possibility to find cancer in the subsequent biopsy is 90%,” Dr Paciucci said. “Currently, the diagnosis of cancer is made only when the cancer lesion is seen in the biopsy.”

By adding the analysis of PTOV1, the positive predictive value of all samples, including those with a score of less than 100, is 34%, and the negative predictive is more than 95%, she said.