title: Mucinous carcinomas of the colon and rectum show higher rates of microsatellite instability and lower rates of chromosomal instability: a study matched for T classification and tumor location.
abstract: BACKGROUND
  The clinicopathologic significance of mucinous carcinomas (Muc) of the colon and rectum has been widely discussed, but there have been few studies on Muc regarding genetic and epigenetic alterations. The current study analyzed genetic and epigenetic alterations of Muc to clarify their differences from well differentiated adenocarcinomas (WD).
  
  
  METHODS
  Thirty-nine cases of Muc and 39 cases of WD were investigated. Cases of WD were matched with cases of Muc for T classification and tumor location. Microsatellite instability (MSI) status and loss of heterozygosity (LOH) of four loci (2p, 5q, 17p, 18q) were evaluated. The methylation status of the hMLH1 promoter region in Muc was also examined.
  
  
  RESULTS
  "MSI tumors" were defined as those that showed MSI-high, and "chromosomal instability (CIN) tumors" were defined as those that showed LOH but not MSI-high. MSI tumors were significantly more frequent in Muc (30.8%) than in WD (5.1%). CIN tumors were significantly less frequent in Muc (53.8%) than in WD (87.2%). In Muc, MSI tumors were significantly more frequent in the proximal colon (55.6%) than in the distal colon (9.5%). Also, methylation of the hMLH1 promoter region in Muc was significantly more frequent in MSI tumors (83.3%) than in CIN tumors (27.8%) (P = 0.0077).
  
  
  CONCLUSIONS
  When matched for T classification and tumor location, Muc shows higher rates of MSI and lower rates of CIN than WD.. Muc shows different characteristics according to tumor location, and methylation of the hMLH1 promoter region strongly correlates with Muc tumors showing MSI.
authors.affiliation: Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. ykazama-tky@umin.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kazama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tada
authors.forename: Junichiro
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D016022:Case-Control Studies; D043171:Chromosomal Instability / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008745:Methylation; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1