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Microsatellite alterations in serum DNA of patients with colorectal cancer.

Cell-free DNA in the blood of cancer patients has been shown to harbor microsatellite alterations frequently matching those of the primary tumors. The aim of this study was to assess the prevalence of allelic loss and instability of serum DNA microsatellites in colorectal cancers. DNA extracted from preoperative sera and microdissected tumors of 27 patients with colorectal adenocarcinoma were allelotyped for nine markers on chromosome arms 1p, 5q, 8p, 12p, 15q, 17p, 17q, and 18q. In all tumors, expression of MLH1 and MSH2 was explored immunohistochemically. Microsatellite alterations comprising loss of heterozygosity (LOH) or microsatellite instability (MSI) were present in 26 of 27 (96%) tumors and in 16 of 27 (59%) serum samples. Using stringent criteria, serum MSI was significantly (p < 0.02) more detectable than serum LOH. Of the three patients with high-grade MSI (more than two unstable loci) present in tumor and serum DNA, two had MSH2-negative tumors on immunohistochemical testing. No significant association of tumor stage or clinical outcome with serum microsatellite alterations of LOH or MSI type could be demonstrated. Although the DNA-shedding phenotype of tumors remains to be elucidated, its detection by serum DNA microsatellite analysis seems to be useful for the diagnosis and monitoring of neoplasms, including colorectal cancers with and without MSI.