Biomarker Found to Predict Malignancy Potential of HG-PIN Lesions in the Prostate

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Title: Biomarker Found to Predict Malignancy Potential of HG-PIN Lesions in the Prostate
URL: http://www.pslgroup.com/dg/22082E.htm
Doctor's Guide
May 2, 2008

PHILADELPHIA, Pa -- May 2, 2008 -- Investigators from Spain have found a means of distinguishing between high-grade prostatic intraepithelial neoplasia (HG-PIN) lesions destined to become cancerous and those that will remain benign in men being screened for prostate cancer. Their findings, reported in the May 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, could eliminate the need for unnecessary needle biopsies.

The research team evaluated HG-PIN 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 HG-PIN. The negative control group included 11 patients with bladder cancer who had both their diseased bladder and healthy prostate removed. The study group comprised 50 patients diagnosed with HG-PIN but not prostate cancer. The study group had an average of 2.5 biopsies each between 2000 and 2004.

Results showed that the expression of the prostate tumour overexpressed gene 1 (PTOV1) in HG-PIN 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.

Finding that PTOV1 gene expression was elevated in HG-PIN associated with cancer, the investigators used tissue microarray and immunohistochemical analyses to see whether PTOV1 protein levels could discriminate these premalignant lesions from HG-PIN 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. Researchers reported that by adding the analysis of PTOV1, the positive predictive value of all samples, including those with a score of <100, is 34% and the negative predictive value is more than 95%.

"This is the first HG-PIN biomarker to be associated with prostate cancer development," said the study's lead author, Rosanna Paciucci, PhD, a researcher at the Vall d´Hebrón Hospital Research Institute in Barcelona, Spain. She said that when the results of this study are validated, the PTOV1 gene marker could be used to determine which men with HG-PIN are at substantial risk of developing prostate cancer.

In most recent studies, the average risk of cancer following a diagnosis of isolated HG-PIN in biopsy ranged from 20% to 30%, the researchers said. And while other researchers have found markers in HG-PIN lesions, none have been able to discriminate among lesions that will progress to cancer.

Dr. Paciucci cautioned that the study results need to be confirmed among a larger study group.

SOURCE: American Association for Cancer Research

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