Reduction of p12 Expression Is a Negative Prognostic Indicator in Patients with Surgically Resected Oral Squamous Cell Carcinoma

Purpose: p12 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12 in oral cancer tissues by immunohistochemistry with clinical and pathological parameters. Experimental Design: Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients’ charts were reviewed for clinical, pathological, and 10-year survival data. Because p12 is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2. Results: Our results showed that strong p12 staining was uniformly seen in normal oral mucosa. p12 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12 staining (<25% of cells stained) correlated with tumor mode of invasion (P 0.001) and higher proliferating cell nuclear antigen (P 0.0028) and CDK2 (P 0.0020) expression. Survival analysis showed significant correlation of low p12 expression with the risk of cervical lymph node metastasis (P 0.001) and patients’ 10-year survival status (P 0.0214). Conclusions: These results allow us to conclude that reduction of p12 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12 expression can be an adjunctive prognostic indicator for patients with oral cancer.