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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer
F A W Coumans1, C J M Doggen2, G Attard3
1Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Research Institute, University of Twente.
Summary
Objects positive for epithelial cell adhesion molecules and cytokeratin (EpCAM+CK+) that are not classified as circulating tumor cells (CTCs) are strong predictors of survival in prostate cancer patients. Higher counts of these EpCAM+CK+CD45- objects correlate with decreased survival.
Area of Science:
- Oncology
- Biomarkers
- Prognostics
Background:
- Circulating tumor cells (CTCs) are established poor prognostic indicators in metastatic carcinomas.
- Many EpCAM+CK+ objects, not meeting strict CTC criteria, may also hold prognostic value.
- This study investigates the survival association of EpCAM+CK+ objects in prostate cancer.
Purpose of the Study:
- To evaluate the prognostic significance of EpCAM+CK+CD45- objects in patients with prostate cancer.
- To determine if these non-CTC EpCAM+CK+ objects can predict patient survival.
- To compare the predictive power of different classes of EpCAM+CK+ objects.
Main Methods:
- Follow-up study of 179 patients with castration-resistant prostate cancer.
- CellSearch system used for isolating EpCAM+ objects and staining for DNA, cytokeratin, and CD45.
- Morphological classification of EpCAM+CK+ objects into seven classes, with survival association analyzed via Kaplan-Meier and Cox regression.
Main Results:
- All EpCAM+CK+CD45- object classes demonstrated a significant association with overall survival (P < 0.001).
- Small tumor microparticles (S-TMP), even without nuclei, were associated with survival outcomes.
- Increased counts of any EpCAM+CK+ object class correlated with reduced survival.
- Prediction models incorporating large tumor cell fragments (L-TCF), age, hemoglobin, and lactate dehydrogenase showed strong predictive value, with S-TMP or CTC performing similarly to L-TCF.
Conclusions:
- EpCAM+CK+CD45- objects, not meeting stringent CTC definitions, serve as robust prognostic markers for survival in prostate cancer.
- These non-CTC EpCAM+CK+ objects provide valuable prognostic information.
- The presence and quantity of these objects are significant indicators of patient outcomes.
