Instability in the Penta-C and Penta-D loci in microsatellite-unstable endometrial cancer

Abstract Endometrial cancer (EC) is the most common gynecologic cancer. Early detection is the most important predictor of survival. The cancer is curable if detected early but the five-year survival rate in advanced cases is only 20%. Microsatellite instability (MSI) testing is frequently used to screen populations for early detection of Lynch syndrome (LS), the most common cause of inherited EC, and to classify EC into distinct groups with unique histological, prognostic, and molecular features. Accurate sample identification is crucial for successful MSI testing because instability is assessed by comparing amplification patterns in markers in the normal and tumor samples that must be taken from the same individual. Penta-C and Penta-D pentanucleotide markers are used widely for sample identification in not only MSI testing but also parentage verification, forensic science, and population genetics studies. We tested 324 pairs of tumor and matched normal DNAs from EC patients for instability in these markers using the Promega MSI Analysis System ™ considered the "gold standard" in MSI testing. Both markers were unstable, and therefore not reliable for MSI testing, in 8.2% of the EC patients with MSI. Instability in both mono- and pentanucleotide markers suggest that the tumors with MSI likely suffer from a "generalized" form of instability affecting other short tandem repeats as well. Results from many studies using these markers for various purposes may not be accurate if samples with MSI are involved.