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Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of
D G Bostwick1, A Pacelli, M Blute
1Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Background:
Prostate specific membrane antigen (PSM) is a membrane-bound antigen that is highly specific for benign and malignant prostate epithelial cells. Its expression in high grade prostatic intraepithelial neoplasia (PIN) has not been compared with that in prostate carcinoma.
Methods:
The authors performed an immunohistochemical study of representative sections from 184 radical prostatectomies from previously untreated patients with pathologic stage T2N0M0 adenocarcinoma treated at the Mayo Clinic between 1987 and 1991. Affinity-purified monoclonal antibody 7E11-5.3 directed against PSM was employed at a concentration of 20 microg/mL overnight. For comparison, serial sections in each case were stained with prostate specific antigen (PSA). Staining for all antibodies was performed using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in increments of 10%. Cox proportional hazards models were used to identify the risk of carcinoma recurrence according to the number of immunoreactive PIN or cancer cells for PSM and PSA; the date of radical prostatectomy was used as the starting time, and serum PSA (biochemical) failure or clinical failure was the event. PSA biochemical failure was defined as serum PSA > 0.2 ng/mL at least 30 days after surgery.
Results:
Intense cytoplasmic immunoreactivity for PSM was observed in the benign and neoplastic epithelial cells in all cases (100% of cases staining). The number of cells staining was lower in benign epithelium and PIN than in adenocarcinoma (69.5+/-17.3% [range, 20-90%] vs. 77.9+/-13.2% [range, 30-100%] vs. 80.2+/-13.7% [range, 30-100%], respectively). With rare exceptions, basal cells were negative, and there was no immunoreactivity of the prostate stroma, urothelium, or vasculature. Adenocarcinoma gave the most intense and extensive staining, and the highest grades of adenocarcinoma (Gleason primary patterns 4 and 5) showed staining in virtually every cell; there was greater heterogeneity of staining in lower grades of adenocarcinoma. By contrast, PSA immunoreactivity was more intense and extensive in benign epithelium than in PIN and adenocarcinoma. The number of immunoreactive PIN or cancer cells for PSM and PSA was not predictive of PSA biochemical or clinical failure as defined in this study.
Conclusions:
PSM was expressed in all cases of prostate adenocarcinoma, with the greatest extent and intensity observed in the highest grades. The expression increased incrementally from benign epithelium to high grade PIN or adenocarcinoma. Conversely, PSA showed the greatest staining in benign epithelium, with decreased expression incrementally from benign epithelium to high grade PIN or adenocarcinoma. Expression of PSM is clinically useful for the identification of prostate epithelium, particularly PIN or adenocarcinoma, and its expression is regulated independent of PSA. The number of PSM immunoreactive cells was not predictive of recurrence, most likely because of the presence of abundant immunoreactivity in most cases, or because of differential expression in primary and metastatic disease.
Insights
Prostate specific membrane antigen (PSM) is highly expressed in prostate cancer, increasing with grade. Unlike prostate specific antigen (PSA), PSM expression is useful for identifying prostate epithelium, including high-grade prostatic intraepithelial neoplasia (PIN) and adenocarcinoma.
Area of Science:
- Uro-oncology
- Immunohistochemistry
- Cancer Biomarkers
Background:
- Prostate specific membrane antigen (PSM) is a prostate-specific membrane antigen.
- Its expression in high-grade prostatic intraepithelial neoplasia (PIN) has not been compared to prostate carcinoma.
Purpose of the Study:
- To compare PSM expression in benign prostate epithelium, PIN, and prostate adenocarcinoma.
- To evaluate the relationship between PSM and prostate specific antigen (PSA) expression.
- To determine if PSM or PSA expression predicts recurrence after radical prostatectomy.
Main Methods:
- Immunohistochemical analysis of 184 radical prostatectomies using anti-PSM and anti-PSA antibodies.
- Quantification of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma.
- Cox proportional hazards models to assess recurrence risk based on PSM and PSA expression.
Main Results:
- PSM was expressed in all prostate adenocarcinoma cases, with increased intensity and extent in higher grades.
- PSM expression increased incrementally from benign epithelium to high-grade PIN and adenocarcinoma.
- PSA expression was highest in benign epithelium and decreased with increasing grade.
Conclusions:
- PSM expression is clinically useful for identifying prostate epithelium, especially PIN and adenocarcinoma.
- PSM expression is regulated independently of PSA.
- PSM expression levels did not predict recurrence in this cohort, likely due to widespread expression.