Gene Expression May Identify High-Risk Prostate Neoplasia

By Charles Bankhead
BARCELONA, 04 may 2008 -- The risk that high-grade prostatic intraepithelial neoplasia will turn malignant may stem from overexpression of a prostate tumor gene, found investigators here.
A negative biopsy finding for overexpression of the gene in high-grade PINs could save men from future biopsies, added the investigators. Conversely, a positive finding could mean quick action.
Malignant high-grade PINs had 60% greater expression of PTOV1 (prostate tumor overexpressed-1) compared with benign lesions, Rosanna Paciucci, Ph.D., of Vall d'Hebron Hospital Research Institute, and colleagues, reported in the May 1 issue of Clinical Cancer Research.
But as expression of PTOV1 decreased, so did the risk of malignant transformation.
If validated in other studies, the findings could help focus prostate biopsy on high-risk high-grade PIN and allow men with benign disease to avoid unnecessary biopsies.
"Those patients with a high PTOV1 score should undergo an immediate repeat biopsy," said Dr. Paciucci. "Men who have low PTOV1 scores might not need additional annoying and useless biopsies. We estimate that we can save 40% of unnecessary biopsies that are repetitively negative and contain high-grade PIN lesions that do not develop into cancer."
Originally identified by Dr. Paciucci and colleagues, PTOV1 and its protein are differentially expressed in prostate cancer and regulated by androgens. Increased expression of PTOV1 correlates with increased proliferative activity and is associated with nuclear localization of POTV1 protein.
Because POTV1 is overexpressed in high-grade PIN associated with cancer, the investigators hypothesized that prostate needle biopsy specimens that test positive for PTOV1 would aid clinical decision making.
To test the hypothesis, Dr. Paciucci and colleagues examined PTOV1 expression in high-grade PIN lesions from 140 patients. Seventy-nine of them had undergone radical prostatectomy for prostate cancer (true positives); 11 had bladder cancer and normal prostate tissue (true negatives); and 50 patients had initial prostate biopsies that contained high-grade PIN but no cancer.
The 50 patients in the study group were followed for an average of 12.4 months, during which time they had an average of 2.5 prostate biopsies. All patients had at least one follow-up biopsy.
For all specimens examined, investigators calculated a histology score based on the percentage of stained cells in a specimen and the intensity of staining. Possible scores could range from 0 to 300.
High-grade PIN in radical prostatectomy specimens had an average score of 162.6 for PTOV1 expression, compared with 67 for specimens from the patients with bladder cancer (P<0.01). In the study group, 11 of 50 patients (22%) had cancer at follow-up, and PTOV1 expression averaged 151.4, whereas the 39 patients with no cancer at follow-up had a mean PTOV1 expression of 94.6 (P<0.01).
PTOV1 expression did not differ between the 11 study patients with cancer at follow-up and the 79 positive controls or between the 39 study patients with no cancer at follow-up and the patients with bladder cancer.
A threshold histology score of 100 for PTOV1 expression resulted in a sensitivity of 90% and a specificity of 57%. A threshold value of 63 was associated with a sensitivity of 95% and a specificity of 38%.
Applying a histology score of 100 to the 50 patients in the study group resulted in a sensitivity of 90.9%, specificity of 51.3%, positive predictive value of 34.5%, and negative predictive value of 95.2%.
Because the study was small and developments in this field, such as PSA velocity, are expanding rapidly, the authors suggest further prospective investigations are needed.
"We suggest that the analysis of PTOV1 expression might be helpful in the follow-up of men with isolated high-grade PIN in biopsies, especially after an extended biopsy scheme," the authors concluded. "An immediate repeated biopsy should be considered if the [histology score] is >100. If cancer is still not detected, the patient would be followed-up for his PSA velocity indicating the need to repeat the biopsy."
The authors reported no disclosures.
Primary source: Clinical Cancer ResearchSource reference:Morote J, et al "PTOV1 expression predicts prostate cancer in men with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy" Clin Cancer Res 2008; 14: 2617-2622.