Proliferative activity and loss of function of tumour suppressor genes as 'biomarkers' in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma

Abstract

Oral cancer is a disease of the elderly and is closely connected with cigarette smoking and alcohol consumption. Since the successful introduction of multidisciplinary treatment, the survival rate has not changed. Because of the high mortality and potentially disfiguring treatment, today's efforts are aimed at eliminating risk factors, chemoprophylaxis, improvement in diagnostic procedures, and understanding of the genetic mechanisms of oral carcinogenesis. Immunohistochemical and molecular biology analysis of biopsy tissue and cell lines of preneoplastic and neoplastic lesions that originate from the oral mucosa have shown that alterations in tumour suppressor genes such as p53 and Rb gene may have an important role in oral carcinogenesis and may be potentially useful prognostic 'biomarkers' in oral carcinogenesis. Statistical analysis of immunohistochemical data from 216 patients did not identify significant or consistent differences of p53, MDM2, or RB expression with respect to stage of disease, malignant transformation, metastatic node involvement, recurrence, or survival. Nevertheless, p53 overexpression seems to correlate strongly with histological progression of the disease, which confirms the importance of p53 alterations in oral carcinogenesis. Overexpression of p53 is usually found in the less differentiated proliferating cells in benign and malignant oral lesions. Assessment of the proliferating activity is possible by immunohistochemical staining with monoclonal antibodies against proliferating nuclear antigen and Ki-67. Statistical analysis shows that overexpression of p53 combined with high proliferative activity predicts a less favourable course of disease in oral squamous cell carcinoma.