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 radiosensitiv ity, in which apoptosis has been shown to play an important role. Rece ntly, 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 th is study, we aimed to determine whether Fas antigen expression is indu ced by radiotherapy for malignant lymphoma and to clarify its possible correlation with the therapeutic effect of radiation therapy. Fifty-s ix patients with tumors of the tongue, oropharynx, and maxillary sinus were examined; four were confirmed as malignant lymphoma, and the res t were identified as squamous cell carcinoma. After obtaining the pati ents' informed consent, biopsies were performed before treatment and a t doses of 4, 10, and 20 Gy of radiotherapy, and specimens were preser ved in liquid nitrogen until further examination. Serial sectioning of 6 mu m was performed using a cryostat, and samples were immunohistoch emically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against Fas. Two of the four patients with malig nant 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 th ese 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 sq uamous cell carcinoma, lymphocytes infiltrating into cancer tissue sho wed Fas antigen expression at 4 Gy of irradiation, and these lymphocyt es disappeared on the tumor tissue at 10 Gy. Therefore, the high radio sensitivity of malignant lymphoma among our samples could be explained by the overexpression of Fas antigen induced by small doses of radiat ion therapy, and Fas ligand could be produced by infiltrating lymphocy tes or may be expressed simultaneously on the lymphoma cells.