title: Unfavorable pathological characteristics in familial colorectal cancer with low-level microsatellite instability.
abstract: A high degree of microsatellite instability (MSI) in colorectal cancer (CRC) is a hallmark of hereditary non-polyposis colorectal cancer (HNPCC), caused by germline defects in the mismatch repair (MMR) genes. A low degree of instability (less than 30% of the microsatellites) is seen in a subset of tumors. To clarify the significance of this low degree of MSI phenotype, we studied the differences between patients with colorectal tumors with high-level, low-level and no MSI. Colorectal tumors with no (n = 68) and low-level (n = 18) MSI of patients clinically suspected of HNPCC were compared to colorectal tumors with high-level MSI (n = 12) of patients that carry a pathogenic germline mutation in a MMR gene. Compared to tumors with no MSI, tumors with low-level MSI were classified more frequently as stage T3 or T4 (100% vs 68% respectively), and showed less immune response (P = 0.02). No significant differences in familial CRC risk were found by comparing pedigrees of these two groups of tumors. Compared to the group of tumors with high-level MSI, the group of tumors with low-level MSI had a less suspicious family history, a higher percentage of lymph node metastasis (56 vs 17%), and less immune response. Thus, with respect to genetic risks, familial CRC can be divided into two groups: Tumors with high-level MSI and tumors with low-level or no MSI. However, tumors with low-level MSI show unfavorable pathological characteristics compared to tumors with no and tumors with high-level MSI. These differences suggest a distinct underlying biology of CRC with low-level MSI.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.kets@antrg.umcn.nl
authors.forename: Carolien M
authors.initials: CM
authors.lastname: Kets
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Danielle
authors.initials: D
authors.lastname: Bodmer
authors.forename: Riki
authors.initials: R
authors.lastname: Willems
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Joannes H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Marjolijn J L
authors.initials: MJ
authors.lastname: Ligtenberg
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D010641:Phenotype
chemical_list: D004273:DNA, Neoplasm