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.