Detection of Clinically Significant, Occult Prostate Cancer Metastases in Lymph Nodes Using a Splice Variant-Specific RT-PCR Assay for Human Glandular Kallikrein

Abstract

Purpose: 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.Patients and 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).Conclusion: 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.