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.
Highlights
Metastatic castrate-resistant prostate cancer is the second deadliest cancer in men in the Western world [1]
Despite the small patient number, these results suggested that loss of nuclear Eg5 expression may be related to docetaxel resistance
Research has been ongoing identifying prognostic biomarkers and biomarkers predictive for therapy response in prostate cancer (PCa) with improved accuracy compared to established biomarkers such as serum prostate-specific antigen (PSA) levels and Gleason-score, with some success [11]
Summary
Metastatic castrate-resistant prostate cancer (mCRPC) is the second deadliest cancer in men in the Western world [1]. It was concluded that ispinesib is not effective in primary prostate cancer (PCa) due to their low mitotic index, resulting in low Eg5 expression. Considering their similar mechanism of action, an alternative explanation could be that cross-resistance occurs between docetaxel and Eg5-inhibitors. Combining aforementioned findings [14;15;18], initial Eg5 expression of PCa may have been decreased once tumors have become docetaxel resistant. This led to our hypothesis that Eg5 may be a predictive marker for docetaxel response. Based on recent findings that patients with high Gleason-scores respond better to taxane-based therapy [21], we further hypothesize that Eg5 may be a prognostic marker for tumor aggressiveness and clinical outcome
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