DIFFERENTIAL IMMUNOHISTOCHEMICAL STAINING FOR DNA TOPOISOMERASE-II-ALPHA AND TOPOISOMERASE-II-BETA IN HUMAN TISSUES AND FOR DNA TOPOISOMERASE-II-BETA IN NON-HODGKINS-LYMPHOMAS

Topoisomerase II (Topo II) is the target for several chemotherapeutic agents, including doxorubicin and etoposide, termed Topo II poisons. P revious studies from cancer cell lines and clinical specimens attempte d to correlate expression of Topo II with drug sensitivity. Mammalian cells, however, contain two isoforms of Topo II, termed Topo II alpha (subunit molecular weight, 170 kDa) and Topo II beta (subunit molecula r weight, 180 kDa), both of which are sensitive to Topo II poisons. St udies of Topo II alpha in normal cells and tissues are limited, and fe w studies have begun to characterize the beta isoform. This study empl oyed in situ immunohistochemical staining to characterize the tissue d istribution of Topo II alpha in formalin-fixed, paraffin-embedded huma n tissues. A new antibody, confirmed by Western blot, specific to the beta isoform, was also used to characterize its distribution in non-ne oplastic, formalin-fixed, paraffin-embedded human tissues and 33 cases of nonHodgin's lymphomas. Topo II alpha was identified in normal tiss ues with proliferating cells, especially in spermatocytes, germinal ce nters, and proliferative endometrium. Some terminally differentiated t issues, e.g., cerebral cortex, skeletal muscle, and nerve, showed no d etectable Topo II alpha, whereas others, e.g., breast, salivary gland, and kidney, showed rare positive cells. In contrast, Topo II beta was present in all tissues, including fully differentiated tissues, e.g., cerebellum, myometrium, pancreas, as well as in tissues with cell tur nover, e.g., endometrium, skin, and bowel mucosa. In non-Hodgkin's lym phomas, Topo II beta was uniformly present with no change in the inten sity or staining pattern among the tumor subtypes. Topo II alpha may b e distinguished from the beta isoform using immunohistochemical techni ques, which permit precise localization of the enzyme in individual ce lls. Detection of this differential expression between the alpha and b eta isoform of Topo II suggests distinct physiologic roles and might a llow better therapeutic targeting for tumors.