Topoisomerase II alpha mRNA and tumour cell proliferation in non-Hodgkin's lymphoma.
OBJECTIVE
To elucidate potential mechanisms of drug resistance, levels of topoisomerase II alpha mRNA, a target for cytostatic drugs, were measured in cryopreserved tumour tissue from 36 patients with non-Hodgkin's lymphoma. To evaluate the potential association between topoisomerase II alpha and cell proliferation, Ki-67 immunostaining was also assessed.


METHODS
The study population comprised 13 patients with low grade and 20 with high grade non-Hodgkin's lymphoma. Three patients had recurrent disease. Topoisomerase II alpha mRNA was quantitated by using reverse transcription polymerase chain reaction (RT-PCR) and the PCR product measured by using HPLC. The MIB-1 monoclonal antibody was used for Ki-67 immunostaining.


RESULTS
Levels of topoisomerase II alpha mRNA correlated strongly with the Ki-67 labelling index and were higher in high grade than in low grade lymphomas. Patients in complete clinical remission of high grade lymphoma had a higher Ki-67 labelling index and tended to have higher topoisomerase II alpha mRNA levels.


CONCLUSIONS
Although topoisomerase II alpha mRNA levels may be indicative of sensitivity to drugs, it is more likely that they reflect the proliferation status of the cell, which in turn involves a large number of additional molecular systems that influence response to treatment.
Lohri
A
A
Department of Internal Medicine, Kantonsspital Basel, Switzerland.
Reuter
J
J
Gudat
F
F
Herrmann
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D002648:Child; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D004250:DNA Topoisomerases, Type II