Micronuclei in Circulating Tumor Associated Macrophages Predicts Progression in Advanced Colorectal Cancer

Abstract

Micronuclei (MN) are fragments of damaged nucleic acids which budded from a cell’s nuclei as a repair mechanism for chromosomal instabilities, which within circulating white blood cells (cWBCs) signifies increased cancer risk, and in tumor cells indicates aggressive subtypes. MN form overtime and with therapy induction, which requires sequential monitoring of rarer cell subpopulations. We evaluated the peripheral blood (7.5 mL) for MN in Circulating Stromal Cells (CStCs) in a prospective pilot study of advanced colorectal cancer patients (n = 25), identifying MN by DAPI+ structures (<3 µm) within the cellular cytoplasm. MN+ was compared to genotoxic induction, progression free survival (PFS) or overall survival (OS) hazard ratios (HR) over three years. MN were identified in 44% (n = 11/25) of CStCs, but were not associated with genotoxic therapies (p = 0.110) nor stage (p = 0.137). However, presence of MN in CStCs was independently prognostic for PFS (HR = 17.2, 95% CI 3.6–80.9, p = 0.001) and OS (HR = 70.3, 95% CI 6.6–752.8, p = 0.002), indicating a non-interventional mechanism in their formation. Additionally, MN formation did not appear associated with chemotherapy induction, but was correlated with tumor response. MN formation in colorectal cancer is an underlying biological mechanism that appears independent of chemotherapeutic genotoxins, changes during treatment, and predicts for poor clinical outcomes.

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

“…PGCC are generally rare cells in tumor tissues and are morphologically heterogeneous. In the blood, these cells may have a size ranging from 25 µm to 300 µm [ 4 , 5 ]. They may have one atypical nucleus or be multinucleated cells.…”