Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases.
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.
Bostwick
D G
DG
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Pacelli
A
A
Blute
M
M
Roche
P
P
Murphy
G P
GP
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000032:analysis*; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology
D000954:Antigens, Surface; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen