Expression of fas (CD95/APO-1) antigen induced by radiation therapy for diffuse B-cell lymphoma: immunohistochemical study

Most malignant lymphomas show relatively high degrees of radiosensitivity, in which apoptosis has been shown to play an important role. Recently, the Fas (CD95/APO-1)/Fas ligand system has been identified as a key regulator of apoptosis in some types of lymphoma cell lines. In this study, we aimed to determine whether Fas antigen expression is induced by radiotherapy for malignant lymphoma and to clarify its possible correlation with the therapeutic effect of radiation therapy. Fifty-six patients with tumors of the tongue, oropharynx, and maxillary sinus were examined; four were confirmed as malignant lymphoma, and the rest were identified as squamous cell carcinoma. After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and specimens were preserved in liquid nitrogen until further examination. Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against Fas. Two of the four patients with malignant lymphoma showed Fas antigen expression on their tumor tissue at 4 and 10 Gy of radiotherapy. These tumors showed high radiosensitivity and disappeared at a dose of 20 Gy of radiotherapy. In samples from these two patients, DNA ladder formation was identified at 10 Gy. In 52 squamous cell carcinomas, staining for the Fas antigen showed negative or only slightly positive results. However, in one of the cases of squamous cell carcinoma, lymphocytes infiltrating into cancer tissue showed Fas antigen expression at 4 Gy of irradiation, and these lymphocytes disappeared on the tumor tissue at 10 Gy. Therefore, the high radiosensitivity of malignant lymphoma among our samples could be explained by the overexpression of Fas antigen induced by small doses of radiation therapy, and Fas ligand could be produced by infiltrating lymphocytes or may be expressed simultaneously on the lymphoma cells.