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.
Highlights
The National Cancer Registry (NCR 2006) in Peninsula Malaysia recorded oral cancers separately into three different segments that include the lip, mouth and tongue cancers
The expression of murine double minute 2 oncogene (MDM2) was not significantly 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 oral squamous cell carcinoma (OSCC)
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
Summary
The National Cancer Registry (NCR 2006) in Peninsula Malaysia recorded oral cancers separately into three different segments that include the lip, mouth and tongue cancers. Tongue and mouth cancers were ranked 21st and 26th while among the females they were ranked 25th and 19th of all cancers respectively. The expression of wild-type p53 protein is undetectable due to its short half-life. Once mutated; its half-life increases and the protein can be detected by immunohistochemistry (IHC). It was suggested that over-expression of p53 protein is indicative of the presence of p53 mutation [4]. 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. There are only few studies discussing the co-expression of MDM2 with p53 in oral squamous cell carcinoma
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