Reduction of p12(DOC-1) expression is a negative prognostic indicator in patients with surgically resected oral squamous cell carcinoma

Purpose: p12(DOC-1) is a growth suppressor that negatively regulates cyclin -dependent kinase 2 (CDK2) activities. Expression of p12(DOC-1) is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12(DOC-1) in oral cancer tissues by immunohistochem istry 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 revi ewed for clinical, pathological, and 10-year survival data. Because p12(DOC -1) is a growth suppressor and associates with CDK2, parallel immunostainin g 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(DOC-1) staining was uniformly s een in normal oral mucosa. p12(DOC-1) staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12(DOC-1) staini ng (< 25% of cells stained) correlated with tumor mode of invasion (P = 0.0 01) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of l ow p12(DOC-1) 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(DOC-1 ) protein expression is a frequent event in oral cancers. Intratumor immuno histochemical evaluation of p12(DOC-1) expression can be an adjunctive prog nostic indicator for patients with oral cancer.