Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy.
OBJECTIVE
It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and beta-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease.


METHODS
Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) >0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade.


RESULTS
Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P=0.010) and for MSP was 0.63 (P=0.004). On multivariable analysis, both CRISP-3 (P=0.007) and MSP (P=0.002) were associated with recurrence. The hazard ratio among CRISP-3-positive/MSP-negative patients compared with CRISP-3-negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781.


CONCLUSIONS
We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.
Bjartell
Anders S
AS
Departments of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. bjartela@mskcc.org
Al-Ahmadie
Hikmat
H
Serio
Angel M
AM
Eastham
James A
JA
Eggener
Scott E
SE
Fine
Samson W
SW
Udby
Lene
L
Gerald
William L
WL
Vickers
Andrew J
AJ
Lilja
Hans
H
Reuter
Victor E
VE
Scardino
Peter T
PT
D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D029584:Prostatic Secretory Proteins / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D012471:Salivary Proteins and Peptides / Q000235:genetics* / Q000378:metabolism; D029589:Seminal Plasma Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
C489926:CRISP3 protein, human; D029584:Prostatic Secretory Proteins; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins; C043076:beta-microseminoprotein