Changes in telomerase activity of advanced cancers of oral cavity and oropharynx during radiation therapy: correlation with clinical outcome.

Telomerase activity has been evaluated for many kinds of malignancies, and it has been clarified that the activity reflected the malignant potential of the tumor. With regard to radiation therapy for cancer, simple and reliable assays for the prediction of therapeutic effect have not been fully developed yet. Therefore, we aimed to determine whether telomerase activity is changed by radiotherapy for advanced head and neck malignancies, and to clarify the possible correlation of telomerase activity with the therapeutic effect of radiation therapy and patients' clinical outcomes. Twenty-five patients with advanced cancers of the oral cavity and oropharynx were examined. All the cancers were confirmed histopathologically as squamous cell carcinomas. Biopsies were performed before treatment and at doses of 4 and/or 10 Gy, and 20 Gy of radiotherapy. To semi-quantitate telomerase activity, a highly sensitive PCR-based telomeric repeat amplification protocol assay was performed. Nineteen of the 21 cancers (90.1%) showed telomerase activity of varied extents prior to radiation therapy. Nine of the 25 patients showed continuous elevations of telomerase activity (> 10 TPG units/microg protein) in their tumors during radiation therapy, and these nine showed 13.8-216.9 TPG units/microg protein at 20 Gy of radiotherapy. In eight of the nine patients, tumors did not respond well to radiotherapy and relapsed locally in a short period after the treatment. On the other hand, in another group of 11 patients, who showed low (< 10) and/or no activity of telomerase in their tumors at 20 Gy of radiotherapy, there were nine patients whose tumors responded well to radiotherapy (p < 0.025 by the chi2 test). None of them relapsed locally in the follow-up period of approximately 21 months, and the difference was statistically significant (p < 0.025 by the chi2 test). It is concluded that the high activity of telomerase in tumor tissue at 20 Gy of radiotherapy can predict a poor therapeutic effect of radiation therapy and unfavorable patients' outcomes for advanced cancers of oral cavity and oropharynx.