Prostate-specific antigen (protein and mRNA) analysis in the differential diagnosis and staging of prostate cancer.
We analyzed complexed and free prostate-specific antigen (PSA), the free/total PSA and complexed/free PSA ratios, acid phosphatase, and prostatic phosphatase in serum from 36 patients with prostatic carcinoma and from 48 non-neoplastic control patients (20 with prostatitis and 28 with benign prostatic hyperplasia). Receiver-operating characteristic plots showed that serum PSA was the most efficient variable, singly used, in discriminating neoplastic from non-neoplastic patients. At a cut-off value of 10.0 ng/ml, serum PSA had a diagnostic sensitivity of 87% and a diagnostic specificity of 83%. In particular, three patients with prostatic carcinoma and twenty non-neoplastic controls had serum PSA levels of between 4 and 10 ng/ml. The subsequent analysis of the serum free/total PSA ratio, in this subgroup, using a cut-off level of 15%, allowed us to classify correctly all prostatic cancer cases and 18/20 non-neoplastic diseases. We next analyzed PSA mRNA in circulating cells using an improved reverse-transcriptase polymerase chain reaction dot blot procedure, from six patients with prostatic carcinoma with distant metastases, and in seventeen with localized cancer. The analysis had a high sensitivity (up to dilutions 1:10(6) of total RNA from prostatic cancer cells vs total RNA from normal blood cells). The analysis revealed circulating micrometastatic cells in 3/6 (50%) cases of metastatic cancer and in 4/17 cases of localized cancer. To conclude, serum total PSA combined with the free/total PSA ratio is a very efficient algorithm in discriminating neoplastic from non-neoplastic prostatic diseases, while other mRNA species must be analyzed, in addition to PSA mRNA, in circulating cells to increase the efficiency in detecting metastatic prostatic cancer.
Castaldo
G
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy.
Cecere
G
G
di Fusco
V
V
Prezioso
D
D
d'Armiento
M
M
Salvatore
F
F
D003937:Diagnosis, Differential; D006801:Humans; D007536:Isomerism; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000097:blood*; D011470:Prostatic Hyperplasia / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011472:Prostatitis / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017430:Prostate-Specific Antigen