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Radioresistance and p53 status of T2 laryngeal carcinoma. Analysis by immunohistochemistry and denaturing gradient
A Kropveld1, P J Slootweg, A D van Mansfeld
1Department of Otorhinolaryngology, University Hospital, Utrecht, The Netherlands.
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 patients with T2 laryngeal carcinoma and recurrent disease after curative therapy. The control group consisted of 16 patients with T2 laryngeal carcinoma without recurrent disease. The p53 gene (exons 5 to 9) was analyzed by Denaturing Gradient Gel Electrophoresis (DGGE). Expression of p53 in biopsy material was visualized by immunohistochemistry (monoclonal antibody BP 53-12-1).
Results:
The group with recurrent disease showed a mutation in 9 cases (45%) and overexpression in 14 cases (70%). In 17 cases (85%) either mutation or overexpression was found. The control group showed a mutation in 7 cases (44%) and overexpression in 14 cases (88%). In 14 cases (88%) either mutation or overexpression was found. Adding up both groups a discordance of 50% was found between both detection techniques. The same mutated exon was found in 6 patients (66%) in both primary and recurrent tumors.
Conclusions:
A discordance between immunohistochemistry and DGGE exists in 50% of the cases. Assuming that both p53 mutation and p53 overexpression are indicative of a disturbed p53 checkpoint system, 31 cases (86%) in both groups show an alteration of the p53 system. No significant difference in p53 status in patients with or without recurrent disease exists. Analysis of the p53 status is not of prognostic significance for irradiation as primary treatment.