Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy.
OBJECTIVE
The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).


METHODS
Tumour material from the colorectal primary carcinomas was analysed for 43 patients. MSI analysis was carried out and immunohistochemistry was performed with hMLH1 and hMSH2.


RESULTS
Tumours of 7 patients (16%) were highly instable (MSI-H). These patients had a better response rate (72% vs. 41%; p = 0.072) and a significantly better median survival (33 months, [95% CI 20-46] vs. 19 months, [95% CI 10-28]; p = 0.021) than microsatellite stable (MSS) patients (n = 36). Furthermore, MSI status was shown to be an independent predictive marker for survival (p = 0.037).


CONCLUSIONS
These data provide further support for the hypothesis that MSI-H CRC might have a better response and survival than (MSS) CRC in palliative first-line treatment.
Brueckl
W M
WM
Department of Internal Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. wolfgang.brueckl@med1.imed.uni-erlangen.de
Moesch
C
C
Brabletz
T
T
Koebnick
C
C
Riedel
C
C
Jung
A
A
Merkel
S
S
Schaber
S
S
Boxberger
F
F
Kirchner
T
T
Hohenberger
W
W
Hahn
E G
EG
Wein
A
A
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins; D010166:Palliative Care; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D015996:Survival Rate; D016896:Treatment Outcome
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D002955:Leucovorin; D005472:Fluorouracil