Microsatellite alterations in serum DNA of patients with colorectal cancer

Cell-free DNA in the blood of cancer patients has been shown to harbor micr osatellite alterations frequently matching those of the primary tumors. The aim of this study was to assess the prevalence of allelic loss and instabi lity 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, 17q, 17q, and 18q. In all tumors, expression of MLH1 and MS H2 was explored immunohistochemically. Microsatellite alterations comprisin g loss of heterozygosity (LOH) or microsatellite instability (MSI) were pre sent in 26 of 27 (96%) tumors and in 16 of 27 (59%) serum samples. Using st ringent criteria, serum MSI was significantly (p < 0.02) more detectable th an serum LOH. Of the three patients with high-grade MSI (more than two unst able loci) present in tumor and serum DNA, two had MSH2-negative tumors on immunohistochemical testing. No significant association of tumor stage or c linical outcome with serum microsatellite alterations of LOH or MSI type co uld 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 color ectal cancers with and without MSI.