title: Elevated microsatellite alterations at selected tetranucleotides in early-stage colorectal cancers with and without high-frequency microsatellite instability: same, same but different?
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.
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.|Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Watson
authors.affiliation: Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger, Norway.|Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Dordi
authors.initials: D
authors.lastname: Lea
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Emma
authors.initials: E
authors.lastname: Rewcastle
authors.affiliation: Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger, Norway.|Centre for Organelle Research (CORE), University of Stavanger, Stavanger, Norway.
authors.forename: Hanne R
authors.initials: HR
authors.lastname: Hagland
authors.affiliation: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.|Gastrointestinal Translational Research Unit, Molecular Laboratory, Hillevåg, Stavanger University Hospital, Stavanger, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Søreide
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
keywords: Colorectal cancer; elevated microsatellite alterations; microsatellite instability; node status; survival