title: Sporadic colorectal carcinomas with low-level microsatellite instability: a distinct subgroup with specific clinicopathological and molecular features.
abstract: OBJECTIVE
  The biologic significance of low-level microsatellite instability (MSI) in sporadic colorectal cancers (CRCs) is not clearly defined. In particular, the relationship of MSI-low to MSI-high and microsatellite stable (MSS) tumours is currently under debate and the prognostic impact of these genetic changes remains unclear. The objective of this study was to investigate whether sporadic MSI-low CRCs have different clinicopathological and molecular features from MSS and MSI-high tumours.
  
  
  METHODS
  A series of 184 primary sporadic CRCs were divided, according to the level of MSI, into three groups (94 MSS, 22 MSI-low and 68 MSI-high) and were analyzed for baseline clinicopathological features and outcome, allelic losses at 18q, 8p and 4p chromosomes and immunohistochemical expression of MGMT, hMlh1, hMsh2, Fhit, Cox-2, p21 and p27 proteins.
  
  
  RESULTS
  MSI-low tumours were more frequently distal (59.1%) whereas MSS tumours had a strong predilection for distal (72.3%) and MSI-high tumours for proximal location (54.4%; p = 0.003). When compared with MSI-high tumors, MSI-low CRCs were adenocarcinoma, not otherwise specified (p = 0.0138) and well to/moderately differentiated (p = 0.027). MSI-low CRCs also showed specific molecular features including intermediate 18q allelic losses, altered MGMT and Cox-2 expression. Finally, the 5-year overall survival rates were 79% for MSI-low, 40.3% for MSS and 71% for MSI-high CRCs (p = 0.0160 MSS vs. MSI-low groups).
  
  
  CONCLUSIONS
  Sporadic MSI-low CRCs display characteristic clinicopathological and genetic features that distinguish them from MSS CRCs.
authors.affiliation: Dipartimento di Patologia e Medicina di Laboratorio, Sezione Anatomia Patologica, Università di Parma, Via Gramsci, 14, 43123 Parma, Italy. cinzia.azzoni@unipr.it
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.forename: Lorena
authors.initials: L
authors.lastname: Bottarelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Cecchini
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Sarli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged