P53/MDM2 co-expression correlates with the tumour differentiation in oral squamous cell carcinoma - a retrospective study and a systematic review

Authors

  • Y.F. Choon Department of Oral Pathology, Oral Medicine and Periodontology
  • A. Ramanathan Oral Cancer Research and Coordinating Centre
  • H. Ali Oral Cancer Research and Coordinating Centre
  • W.M.N. Ghani Oral Cancer Research and Coordinating Centre
  • S.C. Cheong Oral Cancer Research Team, Cancer Research Initiatives Foundation (CARIF) Sime Darby Medical Centre, 47500, Subang Jaya, Malaysia.
  • R.B. Zain Department of Oral Pathology, Oral Medicine and Periodontology

DOI:

https://doi.org/10.22452/adum.vol18no1.2

Keywords:

Oral squamous cell carcinoma, MDM2, p53, Ki-67, immunohistochemistry, systematic review

Abstract

Background: MDM2 and p53 are involved in a negative feedback loop where p53 regulates MDM2 at the transcriptional level. MDM2, in turn, downregulates p53. This co-ordinated interaction between these proteins is set to play an important role in the regulation of cell cycle progression following DNA damage to cells. The over-expression of both p53 and MDM2 has been reported in various cancers. However there are only few studies discussing the co-expression of MDM2 with p53 in oral squamous cell carcinoma Aim: The purpose of this study was to determine the correlation of co-expression of p53, MDM2, and Ki-67 proteins with clinico-pathological factors in oral squamous cell carcinoma (OSCC) and to conduct a systematic review of the co-expression of p53/MDM2. Method: This is a retrospective descriptive study and a systematic review. Formalin-fixed paraffinembedded tissues from 45 OSCC cases were stained by immunohistochemistry (IHC) for p53, MDM2, and Ki-67 proteins. Results: Immuno-reactivity for p53, MDM2, and Ki-67 was seen in 75.6%, 97.8%, and 62.2% cases of OSCC respectively. The co-expression of p53 and MDM2 (p53/MDM2) was detected in 97.1%, however there was no significant correlation between p53 and MDM2 expression. Notably, p53/MDM2 coexpression was significantly associated with tumour differentiation (p-value = 0.045). The Ki-67LI was not significantly associated with neither MDM2 nor p53/MDM2 co-expression (p-value = 0.268, 0.916 respectively). Conclusion: The expression of MDM2 was not signif icantly associated with p53 expression suggesting that MDM2 expression is mediated by p53-independent pathways or mutated p53 could not induce the expression of MDM2 in this set of OSCCs. The only clinico-pathological parameter that correlates significantly with co-expression of p53/MDM2 is tumour differentiation where it is suggestive that the co-expression of these 2 proteins is indicative of aggressive tumour behavior.

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Published

2011-12-30

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