Alterations in MDM2 expression in esophageal squamous cell carcinoma: Relationship with p53 status Sonia Arora Robin Mathew Meera Mathur Tushar Kant Chattopadhayay Ranju Ralhan Email author Article Received: 22 June 2001 Accepted: 25 July 2001 DOI :
10.1007/BF03032350
Cite this article as: Arora, S., Mathew, R., Mathur, M. et al. Pathol. Oncol. Res. (2001) 7: 203. doi:10.1007/BF03032350
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Abstract 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 p53 gene 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 missense 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.
Keywords MDM2 p53 mutation oncogene esophageal squamous cell carcinoma Abbreviations ESCC esophageal squamous cell carcinoma
MDM2 murine double minute 2
mAb monoclonal antibody
SSCP single strand conformation polymorphism
Contract Grant Sponsor: Council of Scientific and Industrial Research, India.
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Authors and Affiliations Sonia Arora Robin Mathew Meera Mathur Tushar Kant Chattopadhayay Ranju Ralhan Email author 1. Department of Biochemistry All India Institute of Medical Sciences New Delhi India 2. Department of Pathology All India Institute of Medical Sciences New Delhi India 3. Department of Surgery All India Institute of Medical Sciences New Delhi India