Immunohistochemical staining for DNA topoisomerase I, DNA topoisomerase II-alpha and p53 in gastric carcinomas.

New anticancer drugs targeting DNA topoisomerase I (topo I) are showing activity against gastric carcinomas. Laboratory studies have indicated that cells responsive to topo I targeted drugs have elevated levels of topo I, require active DNA replication and may require a functional apoptotic pathway. In this study, we evaluated these potential markers of topo I targeted drug sensitivity in 22 cases of primary gastric carcinoma. By immunohistochemical staining, we observed elevated topo I expression in 15 of 22 neoplasms (68%). By immunohistochemical staining for the proliferation marker DNA topoisomerase II-alpha (topo II-alpha), we observed that 16 of 22 neoplasms (73%) had topo II-alpha indices > than 50 indicating a large number of actively cycling tumor cells. Abnormal p53 expression was observed in 7 of the 22 cases (32%). Of the 22 cases of gastric carcinoma, 8 (36%) had high levels of topo I, a large number of cycling tumor cells and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I.