Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues.
BACKGROUND
Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to androgen deprivation and in androgen-independent tumors. The authors studied the effects of short term (3-month) androgen deprivation on PSMA expression in prostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs), 7E11 and PM2J004.5.


METHODS
The study included patients with clinically localized prostate carcinoma who were prospectively randomized into 1 of 2 treatment groups: 3 months of neoadjuvant androgen deprivation therapy followed by radical prostatectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative formalin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The authors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma. They compared the results of 7E11 with those of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma and also compared the results between the two treatment groups (ADT/RP vs. RP alone).


RESULTS
Both anti-PSMA mAbs stained benign secretory-acinar epithelium, high grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 reacted with a significantly greater percentage of cells (P < 0.001) and with significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was similar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J004.5 was significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001). In the ADT/RP group, the percentage of cells stained and the intensity of staining with 7E11 and PM2J004.5 were significantly greater in prostate carcinoma compared with benign epithelium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RP alone) or pathologic stage (in both the RP-alone and ADT/RP groups) and did not differ between the two treatment groups.


CONCLUSIONS
Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate carcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemical marker of prostate carcinoma in formalin fixed, paraffin embedded tissue.
Chang
S S
SS
George M. O'Brien Urology Research Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Reuter
V E
VE
Heston
W D
WD
Hutchinson
B
B
Grauer
L S
LS
Gaudin
P B
PB
D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000032:analysis / Q000096:biosynthesis*; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012680:Sensitivity and Specificity
D000726:Androgen Antagonists; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II