ABSTRACT
c-myc and p53 genes were frequently deregulated in head and neck squamous cell carcinoma (HNSCC). To determine if the concomitant expression of the two oncogenes might have prognostic value, the survival and free disease time of 140 consecutive HNSCC patients followed up for a median time of 29.9 months was analyzed in the light of p53 and c-myc expression assessed by immunohistochemistry. Positive c-myc and p53 staining was detected respectively in 35.7 and 50.7% of the tumors. Double positivity emerged in 16.4% of the cases. Overall-survival of patients was not associated with the immunoreactivity of p53 or c-myc considered separately or grouped in subsets. Considering only the advanced stages, the concomitant expression of both oncogenes in tumors was associated with worse disease-free survival (P = 0.004) suggesting a role for p53 and c-myc genes in progression of this HNSCC subset. Clinical parameters (presence of lymph nodes, histologic grade and tumor width) remained important indicators of overall survival (OS).
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Biopsy, Needle , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Female , Gene Expression Regulation, Neoplastic , Genes, myc , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Staging , Probability , Proportional Hazards Models , Prospective Studies , Risk Assessment , Sensitivity and Specificity , Survival Analysis , Tumor Suppressor Protein p53/metabolismABSTRACT
The theory of field cancerization in tumors of the head and neck reflects the complex oncogenesis that occurs in this region. The mechanisms that control cell proliferation at the molecular level in epidermoid carcinomas (ECs) of the upper aerodigestive tract are still unclear. Mutations in p53 are the genetic alterations most often detected in ECs of the head and neck and seem to contribute actively to the carcinogenic process triggered by p53 as a tumor-suppressor gene and to its association with tobacco. The objective of the present study was to investigate the expression of p53 protein in epidermoid head and neck carcinomas by immunohistochemistry and its immunohistochemical correlation with other prognostic factors. The study was conducted on 63 consecutive ECs cases not submitted to previous treatment. Specimens of the tumor and of the normal adjacent mucosa were collected during surgery and submitted to immunohistochemical reaction for the determination of the expression of anti-protein p53 antibody (M7001 DAKO A/S, Denmark). Anatomo-clinical and demographic data were not significantly correlated with the presence of lymph node metastases or p53 expression in the tumor or in the adjacent normal mucosa. Tumor localization in the larynx was significantly correlated with p53 expression. Histological grading as grades I,II,III and IV was correlated whith significant p53 expression (p = 0.025). Conclusions: 1) in the studied material obtained from 63 cases of head and neck ECs, we detected a 48 percent rate of immunohistochemically detectable p53 overexpression; 2) we did not detect a relationship between demographic patient data and p53 expression in the tumor or in the normal adjacent mucosa; 3) p53 overexpression was significantly more frequent in ECs material from the larynx; and 4) The presence of 12 cases with p53 overexpression in the normal adjacent mucosa and with a p53-negative tumor is in agreement with the theory of field concerization. Follow-up of this patient series for a longer period of time will permit a better analysis of these values.
