Microsatellite instability in multiple nonfamilial malignancies

Development of multiple tumors of different histopathologic types may suggest a profound generalized genetic defect, such as malfunction of DNA mismatch repair (MMR) mechanism. Defects in this mechanism are best reflected in microsatellite instability (MSI). We aimed to determine the role of MSI in a group of patients with dual malignancies and compared the data with that of patients with a single malignancy. Fifty patients were enrolled in the study, of whom 16 patients developed both solid and hematologic nonfamilial malignancies, 18 patients developed a single matched hematologic malignancy, and 16 a single matched solid malignancy. Five microsatellite markers were replicated by polymerase chain reaction (PCR) after DNA extraction from paraffin-embedded tissue blocks and analyzed by the GeneScan Analysis Software. The MSI-high phenotype was defined as instability in at least 40% of the examined loci. A higher prevalence of MSI-high phenotype was found in patients with dual malignancies (31.3%) compared with patients with single hematologic (5.6%) or solid malignancy (6.3%) (P = 0.0498 and 0.07, respectively). In conclusion, defects in DNA MMR mechanism may have an important role in the development of multiple sporadic nonfamilial malignancies.