Alterations in MDM2 expression in esophageal squamous cell carcinoma: relationship with p53 status.
In view of the significance of MDM2 as a regulator as well as critical target of wild type p53, this study was undertaken to determine the alteration in MDM2 expression in esophageal squamons cell carcinoma (ESCC) and its relationship to clinicopathological parameters as well as p53gene and protein status. Immunohistochemical analysis of MDM2 and p53 proteins on paraffin embedded sections from 64 surgically resected ESCCs and matched histologically normal tissues showed overexpression of MDM2 protein in 23/64 (36%) ESCCs, while the histopathologically normal esophageal tissues did not show detectable level of MDM2 immunoreactivity. Interestingly, MDM2 /p53 + phenotype was observed in 37/64 (58%) cases. None of the cases with p53 mis-sense mutations (12/30, 40%) showed detectable level of MDM2 protein. Missense p53 mutations were significantly associated with discordant p53 + /MDM2 immunophenotype (p= 0.004). The most intriguing feature of the study was accumulation of MDM2 in the absence of detectable p53 in 11% of and overexpression of MDM2 and p53 in 25% of ESCCs, suggesting a p53-independent role for MDM2 in a subset of tumors. These results underscore the involvement of MDM2 in p53-dependent and -independent pathways in the pathogenesis of esophageal cancer in the Indian population.
Arora
S
S
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Mathew
R
R
Mathur
M
M
Chattopadhayay
T K
TK
Ralhan
R
R
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2