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.
Coleman
L W
LW
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Bronstein
I B
IB
Holden
J A
JA
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D004264:DNA Topoisomerases, Type I / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D013194:Staining and Labeling / Q000379:methods; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II