MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma: Association with wild-type p53 accumulation

Giancarlo Pruneri, Lorenzo Pignataro, Nadia Carboni, Stefano Luminari, Pasquale Capaccio, Antonino Neri, Roberto Buffa

Research output: Contribution to journalArticlepeer-review

Abstract

The MDM-2 gene encodes for a nuclear phosphoprotein that binds p53 and inhibits its ability to activate transcription by concealing the p53 activation domain. It has been suggested that MDM-2 overexpression might represent an alternative mechanism by which p53-mediated pathways are inactivated in human tumors. MDM-2 overexpression can be detected by immunohistochemical analysis as a result of gene amplification and/or increased mRNA expression. We studied MDM-2 gene amplification and protein overexpression in 46 and 50 cases, respectively, of laryngeal squamous cell carcinomas previously analyzed for p53 gene alterations. Not one of the cases showed MDM-2 gene amplification, whereas MDM-2 nuclear immunoreactivity was found in 17 tumors (34%). In 10 of these, coexpression of p53 protein was detectable in the absence of gene mutations in exons 5 through 9 (P = .03). Likewise, MDM-2 was also overexpressed in 18 (46%) of 39 morphologically normal mucosa samples, 15 (50%) of 30 preneoplastic lesions, and 9 (40%) of 22 cases of severe dysplasia. Finally, we found no significant correlations between MDM-2 expression (neither per se nor in assocciation with wild-type or mutated p53), and the evaluated clinicopathologic parameters of histologic grade, lymph node status, or clinical stage. Our results suggest that MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2 protein overexpression might represent an alternative mechanism by which p53 is inactivated in the early stages of laryngeal cancer tumorigenesis.

Original languageEnglish
Pages (from-to)785-792
Number of pages8
JournalModern Pathology
Volume10
Issue number8
Publication statusPublished - Aug 1997

Keywords

  • Immunohistochemistry
  • Laryngeal cancer
  • MDM-2
  • P53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma: Association with wild-type p53 accumulation'. Together they form a unique fingerprint.

Cite this