Abstract
BackgroundHigh circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC.MethodsIn two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher’s exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts.ResultsIn this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67-positive CTC (p = 0.228), but OS was significantly reduced in the Ki67-positive CTC group (median 512 days vs 751 days, p = 0.0091). No changes in relative proportion of vimentin- or Ki67-positive CTCs were observed in post-treatment samples compared to baseline.ConclusionsAnalysis of vimentin and Ki67 expression can straightforwardly be assessed in CTCs from patients with mCRPC. Poorer survival outcomes were observed in vimentin- and Ki67-positive CTC patients.Translational study protocolsCEC-CTC (IDRCB2008-AOO585-50) and Petrus (NCT01786031).Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2192-6) contains supplementary material, which is available to authorized users.
Highlights
High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently Circulating tumor cells (CTCs) number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer
93 patients in total were recruited: 63 patients were vimentin CTC-negative at baseline and 30 patients were vimentin CTC-positive (≥1 vimentin-positive CTC) (Tables 1 and 3, Fig. 1a). Both vimentin patient cohorts had similar baseline characteristics, other than an increase in visceral/multiple metastatic sites for patients in the vimentin CTC-positive group (43.3 vs 30.2 %) which was consistent with more patients in this group reported to be receiving at least a 3rd line of systemic treatment (40 vs 22.2 %) (Table 1)
Here we show that routine clinical testing of vimentin and Ki67 expression in CTC derived from metastatic castrate-resistant prostate cancer (mCRPC) patients is feasible
Summary
High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Circulating tumor cells (CTCs), captured as a ‘liquid biopsy’ from blood for enumeration and biological characterization of cancers, have the potential to replace biopsy and provide important clinical information on prognosis, therapeutic choice, and drug resistance, while being of interest for drug development and biomarker discovery. They may represent an alternative source of tumor tissue which is accessible using a simple blood test, allowing longitudinal monitoring of tumor aggression and biology at different timepoints to guide therapeutic decisions in a patient’s treatment course [1,2,3]. The detection of Ki67 in CTCs has been previously reported using a microfluidic CTC detection method, offering the opportunity to assess if longitudinal quantification of proliferative and non-proliferative subpopulations may be more clinically informative than examination of total CTC count and/or biopsy alone [18]
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