Relationship between MDM2 and p53 alterations in colorectal cancer and their involvement and prognostic value in the Tunisian population.
BACKGROUND
The prevalence of p53 mutations in colorectal cancer could reach 90%. The most important regulator of this protein that was identified originally was the Murine Double Minute2 (MDM2) oncoprotein, by which the levels of p53 were fixed through an autoregulatory feedback loop. In cancer cases, the overexpression of MDM2 deregulates this feedback, and the signaling pathway between MDM2 and p53 is blocked.


METHODS
We genotyped 167 patients and 167 healthy blood donors to determinate the mutational status of MDM2 and p53. Immunohistochemical analysis was performed on tumor and normal mucosa.


RESULTS
The MDM2 polymorphism study showed a higher distribution of MDM2 SNP309 in tumors compared with healthy controls. At the same time, the majority of samples with SNP309 indicated a positive expression of MDM2 protein in the tumor. In this case, we found a first significant association between p53 expression and the single-strand conformational polymorphism analysis and a second association between the MDM2 polymorphism and p53 mutation. Moreover, the nuclear overexpression of MDM2 and SNP309 was significantly related to a higher mortality rate.


CONCLUSIONS
In this work we wanted to highlight the role, which is becoming increasingly important, of MDM2. In fact, we conclude that the effects of MDM2 SNP309 may be considered a valuable prognostic marker to predict poor outcome for Tunisian patients with colorectal cancer.
Laboratory of Colorectal Cancer Research UR03ES04, Department of Pathology, Mongi Slim Hospital, La Marsa, Tunis, Tunisia. ines_chaar@hotmail.com
Ines
I
Chaar
Sameh
S
Amara
Mariem
M
Khiari
Donia
D
Ounissi
Monia
M
Dhraif
Abd E M
AE
Ben Hamida
Lassad
L
Gharbi
Sabeh
S
Mzabi
Saadia
S
Bouraoui
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014416:Tunisia
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2