Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin.
BACKGROUND
The aim was to determine the values of p53 tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX).


METHODS
This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations.


RESULTS
In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19-0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04-0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX.


CONCLUSIONS
Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.
Zaanan
A
A
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
Cuilliere-Dartigues
P
P
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Pathology.
Guilloux
A
A
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre.
Parc
Y
Y
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris.
Louvet
C
C
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
de Gramont
A
A
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Medical Oncology.
Tiret
E
E
UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of General and Digestive Surgery, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris.
Dumont
S
S
Institut Fédératif de Recherche65, UPMC Univ Paris 06.
Gayet
B
B
Department of Digestive Disease Medical Surgery.
Validire
P
P
Department of Pathology, Institut Mutualiste Montsouris, University Paris Descartes, Paris, France.
Fléjou
J-F
JF
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre; Department of Pathology.
Duval
A
A
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre.
Praz
F
F
INSERM, UMR_S 938, Saint-Antoine Research Centre; UPMC Univ Paris 06, UMR_S 938, Saint-Antoine Research Centre. Electronic address: francoise.praz@upmc.fr.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology
D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil