Elevated microsatellite alterations at selected tetranucleotides in early‐stage colorectal cancers with and without high‐frequency microsatellite instability: same, same but different?. (6th April 2016)

• Record Type: Journal Article
• Authors: Watson, Martin M.; Lea, Dordi; Rewcastle, Emma; Hagland, Hanne R.; Søreide, Kjetil
• Is Part Of: Cancer medicine. Volume 5:Number 7(2016:Jul.)
• Page Start: 1580
• Page End: 1587
• Publication Date: 2016-04-06
• Subjects: Colorectal cancer -- elevated microsatellite alterations -- microsatellite instability -- node status -- survival; 616.994005
• DOI: 10.1002/cam4.709
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Microsatellite instability (MSI) is associated with better prognosis in colorectal cancer (CRC). Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a less‐understood form of MSI. Here, we aim to investigate the role of EMAST in CRC±MSI related to clinical and tumor‐specific characteristics. A consecutive, population‐based series of stage I–III colorectal cancers were investigated for MSI and EMAST using PCR primers for 10 microsatellite markers. Of 151 patients included, 33 (21.8%) had MSI and 35 (23.2%) were EMAST+, with an overlap of 77% for positivity, (odds ratio [OR] 61; P < 0.001), and 95% for both markers being negative. EMAST was more prevalent in colon versus rectum (86% vs. 14%, P = 0.004). EMAST+ cancers were significantly more frequent in proximal colon (77 vs. 23%, P = 0.004), had advanced t‐stage (T3–4 vs. T1–2 in 94% vs. 6%, respectively; P = 0.008), were larger (≥5 cm vs. <5 cm in 63% and 37%, respectively; P = 0.022) and had poorly differentiated tumor grade (71 vs. 29%, P < 0.01). Furthermore, EMAST+ tumors had a higher median number of harvested lymph nodes than EMAST− (11 vs. 9 nodes; P = 0.03). No significant association was found between EMAST status and age, gender, presence of distant metastases or metastatic lymph nodes, and overall survival. A nonsignificant difference toward worse survival in node‐negative colon cancers needs confirmation in larger cohorts. EMAST+ cancers overlap and share features with MSI+ in CRC. Overall, survival was not influenced by the presence of EMAST, but may be of importance in subgroups such as node‐negative disease of the colon. Abstract : Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a form of microsatellite instability that occurs in up to a quarter of colorectal cancers without traditional microsatellite instability (MSI). Presence of EMAST was not prognostic in this cohort of early colorectal cancer (CRC). A trend toward reduced cancer‐specific survival was found for stage II colon cancers with EMAST.