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Clinical Cancer Research Vol. 7, 2776-2782, September 2001
© 2001 American Association for Cancer Research

Regular Articles

Reduction of p12DOC-1 Expression Is a Negative Prognostic Indicator in Patients with Surgically Resected Oral Squamous Cell Carcinoma1

Satoru Shintani2, Mariko Mihara2, Nagaaki Terakado, Yuuji Nakahara, Tomohiro Matsumura, Yohko Kohno, Hiroe Ohyama, Jim McBride, Ralph Kent, Randy Todd, Takanori Tsuji and David T. W. Wong3

Laboratory of Molecular Pathology, Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine [Y. K., H. O., J. M., R. T., T. T., D. T. W. W.]; The Forsyth Institute [R. K.], Boston, Massachusetts 02115; and Department of Oral and Maxillofacial Surgery II, Okayama University Dental School, Okayama 700, Japan [S. S., M. M., N. T., Y. N., T. M.]

Purpose: p12DOC-1 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12DOC-1 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12DOC-1 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 p12DOC-1 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 p12DOC-1 staining was uniformly seen in normal oral mucosa. p12DOC-1 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12DOC-1 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 p12DOC-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 p12DOC-1 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12DOC-1 expression can be an adjunctive prognostic indicator for patients with oral cancer.




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Copyright © 2001 by the American Association for Cancer Research.