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MDM2 expression in areca quid chewing-associated oral squamous cell carcinomas in Taiwan
J S Huang1, T J Ho, C P Chiang
1School of Dentistry, College of Medicine, National Taiwan University, Taipei.
Abstract:
MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of human tumors via inhibition of the p53 tumor suppressor protein. To investigate the potential involvement of MDM2 overexpression in the pathogenesis of oral squamous cell carcinomas (SCCs) in Taiwan, we examined the expression of MDM2 protein and its relationship to p53 protein levels in 52 oral SCCs using antibodies to MDM2 and p53. Of the 52 patients, 36 (69 %) had tumors with positive MDM2 nuclear staining and 32 (61%) had tumors with p53 nuclear staining. Co-expression of MDM2 protein and p53 was detected in 25 (48%) cases; and 9 (17%) tumors showed neither MDM2 protein nor p53 staining. A significant correlation was observed between MDM2 protein and p53 expression in 38 cases with an areca quid (AQ) chewing habit (P=0.032). No significant correlation was found between the degree of MDM2 protein staining and the patients' ages, sex, cancer location, clinical staging, primary tumor TNM status or histological differentiation of SCC at the time of initial presentation. Kaplan-Meier analysis showed that either MDM2 protein expression or co-expression of p53 and MDM2 protein did not relate significantly to patient overall survival. Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.
Insights
Murine double minute gene 2 (MDM2) overexpression is common in oral squamous cell carcinomas, particularly in Taiwanese areca quid chewers. While MDM2 and p53 co-expression occurred frequently, it did not impact patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Murine double minute gene 2 (MDM2) overexpression inhibits the p53 tumor suppressor protein, contributing to human tumor development.
- Oral squamous cell carcinoma (OSCC) is a significant health concern, especially in regions with high rates of areca quid (AQ) consumption.
Purpose of the Study:
- To investigate the expression of MDM2 protein and its relationship with p53 protein levels in Taiwanese oral SCCs.
- To explore the potential role of MDM2 in the pathogenesis of AQ chewing-associated oral SCCs.
Main Methods:
- Utilized immunohistochemistry with antibodies against MDM2 and p53 to examine protein expression in 52 oral SCC samples.
- Analyzed the correlation between MDM2 and p53 expression and clinical-pathological factors, including AQ chewing habits.
- Performed Kaplan-Meier analysis to assess the relationship between MDM2/p53 expression and patient overall survival.
Main Results:
- MDM2 nuclear staining was observed in 69% of tumors, and p53 nuclear staining in 61%.
- Co-expression of MDM2 and p53 was found in 48% of cases.
- A significant correlation between MDM2 and p53 expression was noted in patients with an AQ chewing habit (P=0.032).
- Neither MDM2 expression nor MDM2/p53 co-expression significantly correlated with patient survival.
Conclusions:
- High prevalence of MDM2 overexpression in Taiwanese oral SCCs suggests its involvement in carcinogenesis.
- MDM2 may play a role in the development of AQ chewing-associated oral SCCs.
- Further research is warranted to elucidate the specific mechanisms of MDM2 in oral cancer.