Quantitative polymerase chain reaction does not improve preoperative prostate cancer staging: a clinicopathological molecular analysis of 121 patients.
OBJECTIVE
To improve on current staging and monitoring methods for prostate cancer, we applied the technique of quantitative polymerase chain reaction to measure the degree of tumor burden in the circulation and correlate this with pathological tumor stage. A reproducible, highly sensitive and specific, reverse transcriptase-polymerase chain reaction amplification technique to quantify prostate specific antigen (PSA) and prostate specific membrane antigen gene expression in the peripheral circulation was developed. Using a 32phosphorus-gamma-adenosine triphosphate-5'PSA and prostate specific membrane antigen primer incorporation assay, the ribonucleic acid signal extracted from a single neoplastic cell (LNCaP) premixed in 10 cc normal whole blood could be amplified. PSA and prostate specific membrane antigen polymerase chain reaction indexes have been created for clinical application.


METHODS
From September 1994 through July 1995 specimens from 121 patients were prospectively analyzed for PSA and prostate specific membrane antigen signals.


RESULTS
Circulating PSA producing cells were present in 29 of 33 patients (88%) with metastatic prostate cancer. Two of 19 patients (11%) with no known prostate cancer exhibited positive signals (1 later had prostate cancer), establishing a sensitivity of 88% and specificity of 94% for our assay. Positive PSA polymerase chain reaction signals were detected in 30 of 51 patients (59%) with stages pT1 and pT2 disease and in 13 of 18 (72%) with stage pT3 cancer. No statistically significant relationship of a positive PSA polymerase chain reaction signal to pathological stage, tumor grade, apical involvement or positive surgical margins was found, and no benefit was derived by measuring the quantity of circulating PSA polymerase chain reaction signals. Circulating prostate specific membrane antigen polymerase chain reaction signals were identified mostly in patients with advanced prostate cancer and offered no benefit to preoperative staging.


CONCLUSIONS
Given the high incidence of false positive signals in patients with pathologically determined localized disease, in our experience polymerase chain reaction based assays offer no immediate benefit for preoperative prostate cancer staging. The prognostic significance of detecting circulating prostate specific signals awaits longer followup in this cohort of patients, which is currently under study.
Sokoloff
M H
MH
Department of Surgery, UCLA School of Medicine 90095-1738, USA.
Tso
C L
CL
Kaboo
R
R
Nelson
S
S
Ko
J
J
Dorey
F
F
Figlin
R A
RA
Pang
S
S
deKernion
J
J
Belldegrun
A
A
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D000954:Antigens, Surface / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods*; D011300:Preoperative Care; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D012333:RNA, Messenger; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen