Microsatellite instability and colorectal cancer prognosis.
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.
Benatti
Piero
P
Department of Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena, Italy. p.benatti@unimo.it
Gafà
Roberta
R
Barana
Daniela
D
Marino
Massimiliano
M
Scarselli
Alessandra
A
Pedroni
Monica
M
Maestri
Iva
I
Guerzoni
Laura
L
Roncucci
Luca
L
Menigatti
Mirco
M
Roncari
Barbara
B
Maffei
Stefania
S
Rossi
Giuseppina
G
Ponti
Giovanni
G
Santini
Alessandra
A
Losi
Lorena
L
Di Gregorio
Carmela
C
Oliani
Cristina
C
Ponz de Leon
Maurizio
M
Lanza
Giovanni
G
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
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