DNA-topoisomerase I activity and content in epithelial ovarian cancer.
BACKGROUND
The levels and activity of topoisomerase I were determined in 35 biopsies from patients with ovarian cancer.


METHODS
The activity was defined by the ability to relax supercoiled DNA plasmid, and levels were determined by Western blotting and immunohistochemistry.


RESULTS
We detected topoisomerase I activity in all samples, although at different levels. Enzymatic activity was the same in fresh and frozen tissues. Western blotting analysis detected topoisomerase I in 29 of 35 tumor samples but in the remaining six the levels were below the detection limit. We analyzed the distribution of topoisomerase I in tumor cells and normal infiltrating cells by immunohistochemistry. The enzyme was mainly associated with tumor cells although there were four samples in which tumor cells were negative but in which normal cells, mainly lymphocytes, yielded a positive result.


CONCLUSIONS
The results indicate that topoisomerase I enzymatic activity is detectable in human ovarian tumors, varying among patients. No correlations were found between the levels of the enzyme and its activity. Because of the high heterogeneity observed, enzymatic activity assays should be combined with immunohistochemical evaluation of Topo I in the tumor and normal cells present in the tissue.
Codegoni
A M
AM
Mario Negri Institute for Pharmacological Research, Milan, Italy. mnegri@irfmn.mnegri.it
Castagna
S
S
Mangioni
C
C
Scovassi
A I
AI
Broggini
M
M
D'Incalci
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D003131:Combined Modality Therapy; D004264:DNA Topoisomerases, Type I / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D004264:DNA Topoisomerases, Type I