Related Experiment Videos
Immunohistochemical staining for DNA topoisomerase II in non-Hodgkin's lymphomas
J A Holden1, S L Perkins, G W Snow
1Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Abstract:
DNA topoisomerase II (topo II) is the target of several clinically useful anticancer drugs. Several of these agents, such as doxorubicin and etoposide (VP-16), are used to treat non-Hodgkin's lymphomas (NHL). To understand the therapeutic selectivity of these drugs, a series of 33 cases of NHL for topo II were analyzed using an immunohistochemical technique that detects the enzyme in formalin-fixed, paraffin-embedded tissue. The average topo II index of high grade (Working Formulation) NHL was 48.6 with a range from 24.4 to 79.7. The average topo II index of low grade (Working Formulation) NHL was 4.4 with a range from 0.9 to 11.2. These two values are statistically different (P < .01). The intermediate grade (Working Formulation) NHL are a heterogeneous group based on topo II staining. The average topo II index value for the intermediate grade neoplasms was 26.7 with a range from 1.4 to 54.9. Because the proliferation marker Ki-67 has been shown to be of prognostic importance when used in the analysis of NHL, 27 cases for also were analyzed for MIB1 (Ki-67). The average MIB1 index of the high grade NHL was 59.8 with a range from 40.7 to 80.3. This average is statistically different (P < .01) than the average MIB1 index of 11.2 (range 1.7-28.3) found in the low grade NHL. Similar to results with topo II, the intermediate grade NHL was a heterogeneous group of tumors with respect to MIBI staining and had an average MIB1 index of 49.1 with a range from 8.9 to 86.7. These results show that high grade NHL have topo II and MIB1 indices that are significantly higher than low grade NHL. Intermediate NHL are more heterogeneous and have topo II and MIB1 indices that range from low to high.
Insights
High-grade non-Hodgkin's lymphomas (NHL) show significantly higher DNA topoisomerase II (topo II) and Ki-67 (MIB1) levels than low-grade NHL. Intermediate-grade NHL exhibit heterogeneous expression of these markers, impacting therapeutic selectivity.
Area of Science:
- Oncology
- Molecular Biology
- Immunohistochemistry
Background:
- DNA topoisomerase II (topo II) is a validated target for anticancer drugs like doxorubicin and etoposide (VP-16).
- These drugs are utilized in treating non-Hodgkin's lymphomas (NHL), necessitating an understanding of their therapeutic selectivity.
- Topo II expression levels may correlate with NHL grade and treatment response.
Purpose of the Study:
- To investigate the expression levels of DNA topoisomerase II (topo II) in different grades of non-Hodgkin's lymphomas (NHL).
- To compare topo II expression with the proliferation marker Ki-67 (MIB1) across NHL grades.
- To assess the potential of topo II and Ki-67 as biomarkers for therapeutic selectivity in NHL treatment.
Main Methods:
- Immunohistochemical analysis of formalin-fixed, paraffin-embedded tissue samples from 33 NHL cases.
- Quantification of DNA topoisomerase II (topo II) index in high, intermediate, and low grade NHL.
- Analysis of MIB1 (Ki-67) proliferation index in a subset of 27 NHL cases.
Main Results:
- High-grade NHL demonstrated significantly higher average topo II indices (48.6) compared to low-grade NHL (4.4) (P < .01).
- High-grade NHL also showed significantly higher MIB1 indices (59.8) than low-grade NHL (11.2) (P < .01).
- Intermediate-grade NHL exhibited heterogeneous topo II and MIB1 expression, ranging from low to high levels.
Conclusions:
- High-grade NHL are characterized by significantly elevated DNA topoisomerase II (topo II) and MIB1 (Ki-67) expression compared to low-grade NHL.
- The heterogeneity in topo II and MIB1 indices within intermediate-grade NHL suggests complex biological behavior.
- These findings support the potential utility of topo II and MIB1 as biomarkers for predicting therapeutic selectivity and guiding treatment strategies in non-Hodgkin's lymphomas.