Prostate-specific antigen and its clinical relation to prostatic acid phosphates in patients with some prostate diseases and development of a method for the estimation of PSA bound to 2M.

number: 
517
English
Degree: 
Imprint: 
Biotechnology
Author: 
Wessal Salman Al-Bundi
Supervisor: 
Dr. Ala H. AL-Omran
Dr. Monther M. Fathi
year: 
2001
Abstract:

Abstract:Seurum levels of Prostate- Specific Antigen (PSA) and prostatic Acid phosphates (PAP) were masured by immunradiometric (IRMA) and colorimetric assays respectivity in sera of 171 men with benign prostatic Hyperplasia (BPH), 67 men with localized prostate cancer (PCa) and 12 men with metastatic PCa. Mean PSA and PAP values differed significantly among all groups included in the this study (P < 0.0001). The two markers showed increased serum levels ,_ patients with (BPH) , 40%, 23.4% and 9.4% higer than cutoff values (4 and 10) ng/ ml for PSA and 4 U/L for PAP.Only 1.5 percent and 4.4 percent of patients with localized PCa had PSA levels lesser than (4 and 10) ng/ ml respectively, and we confirmed that 65 j percent and 23.4 percent of BPH patients had PSA level greater than (4 and 10) ng/ ml respectively , so 10 ng /ml may be the more reliable cutoff value for prostate cancer than 4 ng/ ml. 40 percent of patients with localized PCa had PAP serum levels within normal range (0-4) U/L and no one of patients with metastatic PCa had PSA serum level lesser than cut off values of the two prostate cancer markers and no' significant relation ship was observed between PSA and PAP (r = 0.293), but it become significant with high PSA values (r =0.9). Follow up study following, surgical (Prostatectomy and Trans urethra I resection of prostate, TURP ) and medical i treatment (Finasteride, Proscare) , showed significant decrease in the levels of PSA in patients after all kinds of treatments. We found that PSA is a very good tumor marker for monitoring prostate cancer and surpasses PAP in this regard and PSA may help Physician about the therapeutic responses in this cancer , and the ability of PSA and PSA density (PSAD) to distinguish patients with PCa from those with BPH of 53 men with BPH, 25 men with localized PCa and 5 men with metastatic PCa. Mean PSADs were significantly differed among all groups included in this study (P < 0.05). PSAD was found to increase the specificity of PSA in the detection of prostate cancer. PSA rapidly forms a complex with Alpha2-Macroglobulin (oc2M) in vitro; However, PSA complexed with a2M (PSA –a2M) is not deteted by conventional immunoassays for PSA because it is encapsulated by the a2M. In this study we show that denaturation of PSA – a2M at high pH render, PSA immunoreactive. This finding enabled us to design a dissociation assay for the detection of PSA - ct2M, which was based on the removal of immunoreactive PSA in serum, denaturati on of PSA- ot2M at high pH, and measurement of the released PSA immunoreactivity by conventional immunoassay. The PSA - a2M assay was calibrated with PSA- cc2M standard formed in vitro. The concentration of PSA-a2M in sera correlated with that of total PSA both in PCa and BPH; "however, the ratio of PSA - cc2M in relation to total PSA was higher in BPH than in PCa (P < 0.05). The measurement of the ratio of PSA-cc2M to total PSA in serum improves the diagnostic accuracy for PCa compared with assays for total PSA only.