Improved Detection of Microsatellite Instability in Early Colorectal Lesions

open access

 Abstract
Microsatellite instability (MSI) occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR) tracts. Adenomas from 160 patients, ranging in age from 29–55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega). This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers........

Results

Study population and samples

Patients with a history of cancer were preferentially selected for this study resulting in 32.5% (52/160) of cases having a personal or family history of one or more 1^st or 2^nd degree relatives with colon or other LS-associated cancers. Most were colon cancers (43/52). The other LS-associated cancers were ovarian, uterine and gastric..... 

Discussion

.....MSI testing of polyps has been proposed for the early detection of LS, but is currently not a realistic, cost-effective approach due to low sensitivity in early pre-cancerous lesions. The goal of this study was to investigate whether the use of new LMR markers can increase detection of MSI in adenomas to a level approaching that reported for colorectal carcinomas with current marker systems (i.e., >90% sensitivity) [23]. The use of the LMR panel did significantly increase the sensitivity (100% for this study population) for detection of mismatch repair deficient lesions over currently available marker panels without significantly decreasing specificity. Studies to determine the sensitivity for detection of LS still need to be performed to determine if the higher levels of MSI achieved using the new LMR markers will transform MSI testing into a practical screening tool for pre-cancerous lesions and early detection of LS.