MDM2 gene amplification and protein expressions in colon carcinoma: is targeting MDM2 a new therapeutic option?
The aim of this study was to investigate murine double minute-2 (MDM2) gene copy number changes in colon carcinoma and to correlate these findings with an immunohistochemical analysis of MDM2 protein expression and histopathologic prognostic indicators of the tumors. The study included 80 cases of sporadic colon carcinomas. MDM2 protein expression was assessed by immunohistochemistry, and MDM2 gene status by fluorescence in situ hybridization. MDM2 gene amplification was detected in 18% of the 80 cases examined. A strong correlation was found between MDM2 gene amplification and the presence, intensity, and staining proportion of cytoplasmic MDM2 protein expression (p = 0.01). No correlation was found between MDM2 gene amplification and the well-established histopathologic prognostic factors. Given the correlation with gene amplification, we clearly demonstrated that cytoplasmic expression of MDM2 protein is true and relevant and that this finding has to be taken into account when immunohistochemistry would be used as a screening for MDM2 gene amplification in the near future. Targeting MDM2 could be a new approach in colon cancer therapy. The amplification status could be a predictive factor of the response to MDM2-targeted therapy.
Department of Pathology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. hav_monirath@yahoo.com
Monirath
M
Hav
Louis
L
Libbrecht
Liesbeth
L
Ferdinande
Piet
P
Pattyn
Stephanie
S
Laurent
Marc
M
Peeters
Marleen
M
Praet
Patrick
P
Pauwels
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2