Detection of clinically significant, occult prostate cancer metastases in lymph nodes using a splice variant-specific rt-PCR assay for human glandular kallikrein.
OBJECTIVE
To compare the detection of human glandular kallikrein 2 (hK2) mRNA expression in archival lymph nodes with disease progression, the development of prostate cancer metastases, and mortality in patients undergoing radical prostatectomy for locally advanced nonmetastatic prostate cancer.


METHODS
We evaluated total RNA extracted from fixed, paraffin-embedded, histopathologically normal pelvic lymph nodes, removed at radical prostatectomy, from 199 pT3N0 prostate cancer patients (150 extraprostatic extension only; 49 seminal vesicle involvement) for hK2-expressing cells using a novel reverse transcriptase polymerase chain reaction (RT-PCR)/hK2 assay. Cumulative incidence functions and Cox proportional hazards analyses were performed.


RESULTS
Forty patients (20%) had positive results, 80 patients (40%) had negative results, and 79 patients (40%) had equivocal results. RT-PCR/hK2 status was not associated with any pathologic characteristics (P >.05). In postoperative multivariable models, the RT-PCR/hK2 result was associated with prostate cancer progression (P =.001), development of distant metastases (P =.001), and prostate cancer-specific survival (P =.005). In patients experiencing biochemical progression (n = 33), RT-PCR/hK2 status was a predictor of failure to respond to salvage radiotherapy (P =.002).


CONCLUSIONS
RT-PCR/hK2 can detect biologically and clinically significant occult prostate cancer metastases in histopathologically normal lymph nodes. In patients with locally advanced prostate cancer, RT-PCR/hK2 is strongly associated with prostate cancer progression, failure following salvage radiation therapy, development of clinically evident metastases, and prostate cancer-specific mortality after surgery.
Shariat
Shahrokh F
SF
Baylor Prostate Center, the Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.
Kattan
Michael W
MW
Erdamar
Sibel
S
Nguyen
Cuong
C
Scardino
Peter T
PT
Spencer
David M
DM
Wheeler
Thomas M
TM
Slawin
Kevin M
KM
D000368:Aged; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy; D012669:Seminal Vesicles / Q000473:pathology; D020840:Tissue Kallikreins / Q000032:analysis* / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D020840:Tissue Kallikreins