Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments.
BACKGROUND
The accuracy of prostate-specific antigen (PSA) testing in prostate cancer detection is constrained by low sensitivity and specificity. Dysregulated expression of minichromosome maintenance (Mcm) 2-7 proteins is an early event in epithelial multistep carcinogenesis and thus MCM proteins represent powerful cancer diagnostic markers. In this study we investigate Mcm5 as a urinary biomarker for prostate cancer detection.


METHODS
Urine was obtained from 88 men with prostate cancer and from two control groups negative for malignancy. A strictly normal cohort included 28 men with complete, normal investigations, no urinary calculi and serum PSA <2 ng ml(-1). An expanded control cohort comprised 331 men with a benign final diagnosis, regardless of PSA level. Urine was collected before and after prostate massage in the cancer patient cohort. An immunofluorometric assay was used to measure Mcm5 levels in urine sediments.


RESULTS
The Mcm5 test detected prostate cancer with 82% sensitivity (confidence interval (CI)= 72-89%) and with a specificity ranging from 73 (CI=68-78%) to 93% (CI=76-99%). Prostate massage led to increased Mcm5 signals compared with pre-massage samples (median 3440 (interquartile range (IQR) 2280 to 5220) vs 2360 (IQR <1800 to 4360); P=0.009), and was associated with significantly increased diagnostic sensitivity (82 vs 60%; P=0.012).


CONCLUSIONS
Urinary Mcm5 detection seems to be a simple, accurate and noninvasive method for identifying patients with prostate cancer. Large-scale prospective trials are now required to evaluate this test in diagnosis and screening.
Dudderidge
T J
TJ
Department of Pathology and Cancer Institute, University College London, Rockefeller Building, 21 University Street, London, WC1E 6JJ, UK.
Kelly
J D
JD
Wollenschlaeger
A
A
Okoturo
O
O
Prevost
T
T
Robson
W
W
Leung
H Y
HY
Williams
G H
GH
Stoeber
K
K
D000368:Aged; D018797:Cell Cycle Proteins / Q000652:urine*; D015200:Fluoroimmunoassay; D006801:Humans; D008297:Male; D008405:Massage; D010865:Pilot Projects; D011467:Prostate; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000652:urine*; D012680:Sensitivity and Specificity
D018797:Cell Cycle Proteins; C489423:MCM5 protein, human; D017430:Prostate-Specific Antigen