RADIORESISTANCE AND P53 STATUS OF T2 LARYNGEAL CARCINOMA - ANALYSIS BY IMMUNOHISTOCHEMISTRY AND DENATURING GRADIENT GEL-ELECTROPHORESIS

BACKGROUND. Animal experiments and tumor cell line studies have shown that p53 alterations can cause radioresistance. This has not yet been demonstrated in patient groups. METHODS. We report p53 status in 20 pa tients with T2 laryngeal carcinoma and recurrent disease after curativ e therapy. The control group consisted of 16 patients with T2 laryngea l carcinoma without recurrent disease. The p53 gene (exons 5 to 9) was analyzed by Denaturing Gradient Gel Electrophoresis (DGGE). Expressio n of p53 in biopsy material was visualized by immunohistochemistry (mo noclonal antibody BP 53-12-1). RESULTS. The group with recurrent disea se showed a mutation in 9 cases (45%) and overexpression in 14 cases ( 70%). In 17 cases (85%) either mutation or overexpression was found. T he control group showed a mutation in 7 cases (44%) and overexpression in 14 cases (88%). In 14 cases (88%) either mutation or overexpressio n was found. Adding up both groups a discordance of 50% was found betw een both detection techniques. The same mutated exon was found in 6 pa tients (66%) in both primary and recurrent tumors. CONCLUSIONS. A disc ordance between immunohistochemistry and DGGE exists in 50% of the cas es. Assuming that both p53 mutation and p53 overexpression are indicat ive of a disturbed p53 checkpoint system, 31 cases (86%) in both group s show an alteration of the p53 system. No significant difference in p 53 status in patients with or without recurrent disease exists. Analys is of the p53 status is not of prognostic significance for irradiation as primary treatment. (C) 1996 American Cancer Society.