title: KLK15 is a prognostic marker for progression-free survival in patients with radical prostatectomy.
abstract: In search of biomarkers for prostate cancer, we evaluated the expression of the human kallikrein-related peptidase KLK15 in samples of prostatic adenocarcinomas from radical prostatectomies. Twenty-five pairs of cancerous and adjacent normal prostatic tissue were selected by laser capture microdissection. The tissue was used for quantification of KLK15 mRNA by reverse-transcriptase polymerase chain reaction. Immunohistochemical expression of the KLK15 protein in 193 samples of prostatic adenocarcinoma was analysed in relation to clinicopathological parameters of the patients and disease progression. Expression of KLK15 correlated with the pathological tumour stage and Gleason score of the cases, both at mRNA and at protein level. While mRNA expression in the tumour was elevated, the protein level of KLK15 was reduced compared with adjacent normal tissue and to prostatic intraepithelial neoplasia. Univariate Kaplan-Meier analysis showed a significant association of dichotomised KLK15 levels with disease progression defined by prostate-specific antigen relapse (p = 0.001). Multivariate analysis according to the Cox proportional hazards regression model identified dichotomised KLK15 expression, corrected for the patient parameters age, preoperative prostate-specific antigen level, pathological tumour stage, Gleason score and surgical margin status, as an independent prognostic factor for poor outcome (inclusion model, hazard ratio 1.802, 95% confidence interval 1.037-3.132, p = 0.037). We suggest KLK15 as a new independent tumour marker for patients at risk for disease progression after radical prostatectomy.
authors.affiliation: Department of Urology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rabien
authors.forename: Florian R
authors.initials: FR
authors.lastname: Fritzsche
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.forename: Angelika
authors.initials: A
authors.lastname: Tölle
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C501608:KLK15 protein, human; D007610:Kallikreins