Assessment of the Circulating Tumor Cells and Microsatellite Instability in Colorectal Cancer Patients: Prognostic and Diagnostic Value

Aya Alsayed,1 Salem E Salem,1 Mostafa M El Serafi,1 Mona S Abdellateif,2 Abdel-Rahman N Zekri,3 Marwa Mohanad,4 Abeer A Bahnassy5 1Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt; 2Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt; 3Molecular Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt; 4Biochemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, 12945, Egypt; 5Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, EgyptCorrespondence: Abeer A BahnassyPathology Department, National Cancer Institute, Cairo University, Cairo, EgyptFax +20 223644720Email chaya2000@hotmail.ComBackground: Microsatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients.Methods: CTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates.Results: MSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (< 4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥ 4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P< 0.001), decreased CTC levels during the course of treatment (P< 0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P< 0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P< 0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P< 0.001, P= 0.047, P=0.001 and P< 0.001; respectively).Conclusion: MSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients’ survival rates and outcomes.Keywords: circulating tumor cells, microsatellite instability, colorectal cancer, response to treatment, survival rates