title: Clinicopathologic and pedigree differences in amsterdam I-positive hereditary nonpolyposis colorectal cancer families according to tumor microsatellite instability status.
abstract: OBJECTIVE
  To establish the clinicopathologic and familial differences within Amsterdam I-positive families, showing either tumor microsatellite instability (MSI) or microsatellite stability (MSS) in order to confirm or deny the existence of hereditary nonpolyposis colorectal cancer (HNPCC) without defects in the mismatch repair system.
  
  
  METHODS
  Sixty-four Amsterdam I-positive families were included in the study for which full, three-generation, family medical histories and colorectal paraffin-embedded tumors were obtained. Both personal and clinicopathologic information of patients were collected. In all cases, both the MSI status and the mismatch repair (MMR) protein expression were analyzed. MMR genetic testing was performed on the MSI families.
  
  
  RESULTS
  Of the Amsterdam I-positive families, 59.4% were tumor MSI, and 40.6% were tumor MSS. When comparing both groups, the statistical differences were observed in the age of onset (MSI, 41 years; MSS, 53 years); in the colorectal tumor location, more frequently proximal in MSI cases; in fewer mucinous tumors in MSS; and loss of MMR protein expression in the MSI tumors. Regarding the individual and familial cancer history, we observed a predominance of individuals with multiple primary tumors in MSI pedigrees, as well as differences in the type of tumors developed within the family.
  
  
  CONCLUSIONS
  Our findings support the suspicion of another hereditary colorectal syndrome different from HNPCC and characterized by MSS, the normal MMR immunohistochemical expression, the presence of only colorectal tumors, and the absence of individuals with multiple primary tumors. All these circumstances suggest the existence of a non-MMR gene being responsible for this new syndrome.
authors.affiliation: Familial Cancer Unit, Spanish National Cancer Centre, Melchor Fernández Almagro, Madrid, Spain. lvalle@cnio.es
authors.forename: Laura
authors.initials: L
authors.lastname: Valle
authors.forename: Jose
authors.initials: J
authors.lastname: Perea
authors.forename: Pablo
authors.initials: P
authors.lastname: Carbonell
authors.forename: Victoria
authors.initials: V
authors.lastname: Fernandez
authors.forename: Ana M
authors.initials: AM
authors.lastname: Dotor
authors.forename: Javier
authors.initials: J
authors.lastname: Benitez
authors.forename: Miguel
authors.initials: M
authors.lastname: Urioste
mesh_terms: D000328:Adult; D017668:Age of Onset; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D010375:Pedigree