Protein expression of p53 and Bcl-2 has a strong correlation with radiation resistance of laryngeal squamous cell carcinoma but does not predict the radiation failure before treatment

Abstract

To examine what factors can precisely predict the radio-sensitivity or radio-resistance of early stage laryngeal squamous cell carcinomas (LSCC), protein expression of p53, Bcl-2 and Bax and loss of heterozygosity (LOH) at 3p and 9p loci were investigated. From June 1994 through June 1999, specimens of primary tumors were obtained by biopsy from 21 patients diagnosed as early stage LSCC at Miyagi Cancer Center Hospital under approved protocol. Labeling indexes of p53 and Bcl-2 were markedly increased in the recurrent tumors (n=8) and the differences were significant by statistical analysis (p=0.043 and p=0.015). However, when labeling indexes of the samples before treatment from non-recurrent cases were compared with those of the samples before treatment from recurrent tumors (n=13), no significant difference was observed. When LOH was examined, 16 out of these 21 cases were acceptable for evaluation, 4 of which (25%) had a relapse. Allelic loss at the 9p21 and 3p21 loci was found in 6 of 13 cases (46%) and 10 of 16 cases (63%), respectively. The frequency of LOH at the 3p21 locus in the recurrent cases was 100% (4 out of 4) and that in non-recurrent cases was 50% (6 out of 12). The frequency of LOH in recurrent tumors was apparently higher than that in non-recurrent tumors. Preservation rates of the larynx of the patients with 3p21 LOH negative tumors was very high (100%) and that of the patients with 3p21 LOH positive tumors was low. These results indicate that although expression of p53 and Bcl-2 had a strong correlation with recurrent LSCC treated by irradiation, immunohistochemical analysis of p53 and Bcl-2 in the sample before treatment was not able to predict the radiation failure. Moreover, our results also indicated that molecular research on genetic instability such as allelic loss may be more sensitive for the detection of radio-resistant tumor cells.