Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Niotis Athanasios
Dissertation committee:
Δημήτριος Δημητρούλης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Κωνσταντινίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικόλαος Νικηταίας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Στραβοδήμος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Αδαμάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Αγρογιάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Διερεύνηση της συνέκφρασης των πρωτεϊνών p53 και MDM2 στο αδενοκαρκίνωμα του παχέος εντέρου με ψηφιακή ανάλυση εικόνας
Translated title:
Comparative Expression Analysis of TP53 Tumor Suppressor and MDM2 Oncogene in colorectal adenocarcinoma on digital image analysis
Summary:
The p53 tumor suppressor protein (17p13.1) regulates critically the cell cycle involved thus in cancer initiation and prevention. The gene is frequently mutated in colon carcinoma patients and the mutations have been associated with poor prognosis and response rates to chemotherapy. Our purpose was to correlate p53 expression with MDM2, a proto-oncogene (12q14.3), which acts as a major negative regulator in p53-MDM2 auto-regulatory pathway. Methods: A total of forty (n=40) colon adenocarcinoma cases were included in the study. Immunohistochemistry was applied by using anti-p53 and anti-MDM2 antibodies in the corresponding tissue sections. Additionally, a digital image analysis assay was implemented for measuring objectively p53/MDM2 immunostaining intensity levels. Results: Over expression of p53 protein was observed in 27/40 (67.5%), whereas MDM2 in 28/40 (70%). Interestingly, in 21/40 (52.5%) cases a combined p53/MDM2 co-expression was detected, whereas in 6/40 (15%) a combined loss of expression was identified (overall co-expression: p=0,119). p53 overexression was significantly correlated to grade of the examined cases (p=0.001), whereas MDM2 to stage and max diam of the malignancies (p=0.001, p=0.024, respectively).
Conclusions: p53/MDM2 over expression is a frequent and critical genetic event in colon adenocarcinomas associated with an aggressive biological behaviour (grade/max diam/stage). Accumulation of p53 protein in the nucleus of tumor cells harboring mutant p53 -as the result of it’s over expression- does not mean necessarily decreased expression of MDM2. MDM2 directly binds to p53 and represses its transcriptional activity promoting p53 degradation. Co-expression of the molecules is observed in sub-groups of patients.
Main subject category:
Health Sciences
Keywords:
Colon, Carcinoma, TP53, Mdm2, Immunohistochemistry, Digital image analysis
Number of references:
100
