title: Nuclear Eg5 (kinesin spindle protein) expression predicts docetaxel response and prostate cancer aggressiveness.
abstract: Novel biomarkers predicting prostate cancer (PCa) aggressiveness and docetaxel therapy response of PCa patients are needed. In this study the correlation between nuclear Eg5-expression, PCa docetaxel response and PCa aggressiveness was assessed. Immunohistochemical staining for nuclear Eg5 was performed on 117 archival specimens from 110 PCa patients treated with docetaxel between 2004 and 2012. Samples were histologically categorized as positive/negative. Median follow-up time from diagnosis was 11.6 years. Nuclear Eg5-expression was significantly related to docetaxel response (p=0.036) in tissues acquired within three years before docetaxel initiation. Nuclear Eg5-expression was not related to Gleason-score (p=0.994). Survival of patients after docetaxel initiation did not differ based on nuclear Eg5-expression (p=0.540). Analyzing samples taken before hormonal therapy, overall survival and time to docetaxel use were significantly decreased in patients with nuclear Eg5-expressing tumors (p<0.01). Eg5-positive nuclei were found more frequently in T4-staged tumors (p=0.04), Gleason 8-10 tumors (p=0.08), and in metastasized tumors (p<0.01). Multivariate analyses indicated that nuclear Eg5-expression may be an independent parameter for tumor aggressiveness. Limitations of a retrospective analysis apply. In conclusion, nuclear Eg5-expression may be a predictive biomarker for docetaxel response in metastatic castrate-resistant PCa patients and a prognostic biomarker for hormone-naive PCa patients. Prospective validation studies are needed.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Department of Urology, Leiden University Medical Center, Leiden, the Netherlands. Contributed equally to this work.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Wissing
authors.affiliation: Department of Urology, Erasmus MC-Cancer Institute, Rotterdam, the Netherlands. Contributed equally to this work.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: De Morrée
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vincent O
authors.initials: VO
authors.lastname: Dezentjé
authors.affiliation: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jeroen T
authors.initials: JT
authors.lastname: Buijs
authors.affiliation: Department of Pathology, Reinier de Graaf Gasthuis, Delft, the Netherlands.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: De Krijger
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Urology, Erasmus MC-Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Wytske M
authors.initials: WM
authors.lastname: Van Weerden
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Urology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Gabri
authors.initials: G
authors.lastname: van der Pluijm
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C470243:KIF11 protein, human; D043823:Taxoids; D000077143:Docetaxel; D016547:Kinesins