Immunohistochemical study and molecular assay in oral cancer: A cohort analysis of prognostic factors.

T. Cutilli a MD, E. Altobelli b MD, M. Valenti b Prof. MD, F. Papola c, SD, A. Corbacelli a Prof. MD

a Maxillofacial Surgery Institute - Department of Surgical Sciences - University of LAquila Italy b Statistical Institute - Department of Medicine and Public Health -University of LAquila Italy c Health National Service-Tissue Typing Center of LAquila Italy

AIM - The AA carried out an immunohistochemical and genetic research on p53 tumor suppressor gene and H-ras oncogene in maxillofacial tumors to evaluate the p53 and H-ras status, response to induction chemotherapy, and global survival, keeping up a study performed from many years. METHODS - 25 consecutive cases of squamous cell carcinomas with metastatic nodes were selected on the basis of homogeneous grading (G2). The patients underwent induction chemotherapy (CDDP/5FU), restaging, surgery, and adjuvant radiotherapy. Monoclonal AB, and DNA extraction and PCR amplification were utilized, respectively, for immunohistochemical and genetic analysis of p53 and H-ras. Differences between proportions of contingency tables were assessed by the Fisher Exact Test; correlation analysis was done using Spearmen Correlation Coefficient. Univariate (product limit) and multivariate (proportional hazards model) methods were used to estimate prognostic variables and related death risk. RESULTS - The data show a strong association then between H-RAS overexpression and H-RAS genetic mutations (pFisher =0.000064) that between P53 overexpression and P53 genetic mutations (pFisher =0.000203). A significant inverse correlation was found between P53 overexpression and chemotherapy response (r= -0.892, p= 0.0001). The cumulative survival of the entire cohort at 28 months of follow-up is 28.58% (standard error=10.24%). Percentage of p53 Monoclonal AB linked > 45% is prognostic variable for death risk with relative risk of 8.89 (95% c.i. 2.48-31.90). CONCLUSIONS - These data show that immunohistochemical study should be inserted in the staging system of tumor mostly in the advanced lesions which need multimodality of treatment. Oncogenetic pattern supplies important elements for diagnostic and prognostic evaluation, besides the classical factors of screening, and it may work together in better therapeutic planning.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.