Improved Detection of Microsatellite Instability in Early Colorectal Lesions Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Thursday, September 17, 2015

Improved Detection of Microsatellite Instability in Early Colorectal Lesions



open access
  
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 1st or 2nd 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. About six percent (9/160) of patients had a previous colorectal carcinoma and 78% (7/9) of these had synchronous or metachronous lesions in this study. An additional 11% (18/160) had lesions previously removed. Only 3% (5/160) had both a personal and family history of colon cancer.
A total of 430 lesions from 160 patients were used in this study. The age at polypectomy ranged from 29 to 55 years, with an average age of 47.5 years. The study population consisted of 54% men and 46% women. Most lesions tested were ≥5mm in size. A board-certified pathologist analyzed each lesion. Of the 414 lesions with clear pathological findings, there were 3 hyperplastic polyps, 287 tubular adenomas, 81 tubulovillus adenomas, 8 villous adenomas, 7 traditional serrated adenomas, 7 sessile serrated adenomas, 2 intramucosal carcinomas, and 19 invasive adenocarcinomas......

 One of the more interesting findings from this study was the high proportion of MSI-High adenomas in likely LS cases.

 ....MSI is predominately seen in proximal or right-sided colorectal cancers. This is especially true in sporadic MSI-High cancers where over 90% may be located in the proximal colon [37, 38]. However, right-sided location is less prevalent in LS carcinomas (20–62%) [39, 40] and adenomas (27–51%) [8, 13, 14, 41]. The apparent higher incidence of right-sided carcinomas may be due in part to the more rapid progression of tumors in the proximal colon [41]. In our study, left- and right-sided MSI-High tumors occurred with similar frequencies; however, all four carcinomas were right-sided (Table 2). Based on these findings, it would appear that using right-sided location as a selection criteria for screening adenomas would result in missing a substantial proportion of LS tumors.....

... 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.

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