title: Microsatellite instability and colorectal cancer prognosis.
abstract: OBJECTIVE
  Many studies have evaluated the role of high levels of microsatellite instability (MSI) as a prognostic marker and predictor of the response to chemotherapy in colorectal cancer (CRC); however, the results are not conclusive. The aim of this study was to analyze the prognostic significance of high levels of MSI (MSI-H) in CRC patients in relation to fluorouracil-based chemotherapy.
  
  
  METHODS
  In three different institutions, 1,263 patients with CRC were tested for the presence of MSI, and CRC-specific survival was then analyzed in relation to MSI status, chemotherapy, and other clinical and pathologic variables.
  
  
  RESULTS
  Two hundred and fifty-six tumors were MSI-H (20.3%): these were more frequently at a less advanced stage, right-sided, poorly differentiated, with mucinous phenotype, and expansive growth pattern than microsatellite stable carcinomas. Univariate and multivariate analyses of 5-year-specific survival revealed stage, tumor location, grade of differentiation, MSI, gender, and age as significant prognostic factors. The prognostic advantage of MSI tumors was particularly evident in stages II and III in which chemotherapy did not significantly affect the survival of MSI-H patients. Finally, we analyzed survival in MSI-H patients in relation to the presence of mismatch repair gene mutations. MSI-H patients with hereditary non-polyposis colorectal cancer showed a better prognosis as compared with sporadic MSI-H; however, in multivariate analysis, this difference disappeared.
  
  
  CONCLUSIONS
  The type of genomic instability could influence the prognosis of CRC, in particular in stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival among MSI-H patients. The survival benefit for patients with hereditary non-polyposis colorectal cancer is mainly determined by younger age and less advanced stage as compared with sporadic MSI-H counterpart.
authors.affiliation: Department of Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena, Italy. p.benatti@unimo.it
authors.forename: Piero
authors.initials: P
authors.lastname: Benatti
authors.forename: Roberta
authors.initials: R
authors.lastname: Gafà
authors.forename: Daniela
authors.initials: D
authors.lastname: Barana
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Marino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scarselli
authors.forename: Monica
authors.initials: M
authors.lastname: Pedroni
authors.forename: Iva
authors.initials: I
authors.lastname: Maestri
authors.forename: Laura
authors.initials: L
authors.lastname: Guerzoni
authors.forename: Luca
authors.initials: L
authors.lastname: Roncucci
authors.forename: Mirco
authors.initials: M
authors.lastname: Menigatti
authors.forename: Barbara
authors.initials: B
authors.lastname: Roncari
authors.forename: Stefania
authors.initials: S
authors.lastname: Maffei
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rossi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Santini
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Carmela
authors.initials: C
authors.lastname: Di Gregorio
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ponz de Leon
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D042822:Genomic Instability; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D005472:Fluorouracil