Previously, we reported that about 50% of prostate cancer patients had circ
ulating tumor cells prior to radical prostatectomy regardless of whether th
ey were subsequently found to have stage pT(2) or pT(3) disease, We also ob
served that after neoadjuvant hormone deprivation prior to prostatectomy, o
nly 27% of patients expressed prostate specific membrane antigen (PSMA) by
reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that n
eoadjuvant hormone deprivation decreased the number of patients positive fo
r circulating cells, With a median follow-up of 2 years, we have examined w
hether the presence of circulating cells detected by RT-PCR for PSMA was pr
edictive of subsequent failure, as judged by prostate specific antigen (PSA
), after radical prostatectomy and found that it was not. We had identified
PSMA as a unique folate hydrolase and thus can potentially subject cells t
o folate deficiency. We questioned whether the presence of a thermolabile m
ethylenetetrahydrofolate reductase (MTHFR) may identify a group of patients
whose cancers would have a more aggressive phenotype, We did not find that
patients with the thermolabile MTHFR phenotype were more likely to have di
sease recurrence after radical prostatectomy, Thus, better markers of malig
nant potential are required to identify those patients with prostate cancer
who are destined to have a recurrence after prostatectomy.