Improved Detection of Microsatellite Instability in Early Colorectal Lesions.
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 incre...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0132727 |
| _version_ | 1819040387914792960 |
|---|---|
| author | Jeffery W Bacher Chelsie K Sievers Dawn M Albrecht Ian C Grimes Jennifer M Weiss Kristina A Matkowskyj Rashmi M Agni Irina Vyazunova Linda Clipson Douglas R Storts Andrew T Thliveris Richard B Halberg |
| author_facet | Jeffery W Bacher Chelsie K Sievers Dawn M Albrecht Ian C Grimes Jennifer M Weiss Kristina A Matkowskyj Rashmi M Agni Irina Vyazunova Linda Clipson Douglas R Storts Andrew T Thliveris Richard B Halberg |
| author_sort | Jeffery W Bacher |
| collection | DOAJ |
| description | 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. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001), which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001). The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible. |
| first_indexed | 2024-12-21T09:08:18Z |
| format | Article |
| id | doaj.art-649f3b4de0e94d8aaca74b8230ff0aad |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T09:08:18Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-649f3b4de0e94d8aaca74b8230ff0aad2022-12-21T19:09:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013272710.1371/journal.pone.0132727Improved Detection of Microsatellite Instability in Early Colorectal Lesions.Jeffery W BacherChelsie K SieversDawn M AlbrechtIan C GrimesJennifer M WeissKristina A MatkowskyjRashmi M AgniIrina VyazunovaLinda ClipsonDouglas R StortsAndrew T ThliverisRichard B HalbergMicrosatellite 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. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001), which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001). The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible.https://doi.org/10.1371/journal.pone.0132727 |
| spellingShingle | Jeffery W Bacher Chelsie K Sievers Dawn M Albrecht Ian C Grimes Jennifer M Weiss Kristina A Matkowskyj Rashmi M Agni Irina Vyazunova Linda Clipson Douglas R Storts Andrew T Thliveris Richard B Halberg Improved Detection of Microsatellite Instability in Early Colorectal Lesions. PLoS ONE |
| title | Improved Detection of Microsatellite Instability in Early Colorectal Lesions. |
| title_full | Improved Detection of Microsatellite Instability in Early Colorectal Lesions. |
| title_fullStr | Improved Detection of Microsatellite Instability in Early Colorectal Lesions. |
| title_full_unstemmed | Improved Detection of Microsatellite Instability in Early Colorectal Lesions. |
| title_short | Improved Detection of Microsatellite Instability in Early Colorectal Lesions. |
| title_sort | improved detection of microsatellite instability in early colorectal lesions |
| url | https://doi.org/10.1371/journal.pone.0132727 |
| work_keys_str_mv | AT jefferywbacher improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT chelsieksievers improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT dawnmalbrecht improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT iancgrimes improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT jennifermweiss improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT kristinaamatkowskyj improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT rashmimagni improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT irinavyazunova improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT lindaclipson improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT douglasrstorts improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT andrewtthliveris improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions AT richardbhalberg improveddetectionofmicrosatelliteinstabilityinearlycolorectallesions |