Clinical Research Papers:
Nuclear Eg5 (kinesin spindle protein) expression predicts docetaxel response and prostate cancer aggressiveness
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Michel D. Wissing1,2,*, Ellen S. De Morrée3,*, Vincent O. Dezentjé1, Jeroen T. Buijs2, Ronald R. De Krijger4, Vincent T.H.B.M. Smit5, Wytske M. Van Weerden3, Hans Gelderblom1 and Gabri van der Pluijm2
1 Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands
2 Department of Urology, Leiden University Medical Center, Leiden, the Netherlands
3 Department of Urology, Erasmus MC-Cancer Institute, Rotterdam, the Netherlands
4 Department of Pathology, Reinier de Graaf Gasthuis, Delft, the Netherlands
5 Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
* These authors contributed equally to this work
Michel Wissing, email:
Keywords: biomarker; docetaxel; Eg5; kinesin spindle protein; prostate cancer.
Received: March 9, 2014 Accepted: May 17, 2014 Published: May 19, 2014
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.
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