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Expression of DNA topoisomerase IIalpha in thyroid neoplasia
A Lee1, V A LiVolsi, Z W Baloch
1Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Abstract:
Topoisomerase II (topo II) is an enzyme that affects replication, transcription, and chromosome segregation. It serves as a target for several useful antichemotherapeutic agents, such as etoposide (VP-16) and teniposide (VM26). Monoclonal antibody topo IIalpha (Clone JH2.7; Neomarkers, Union City, CA) specifically identifies the alpha isoform of topo II. Using this antibody in an immunohistochemical analysis, we studied differential expression of topo II in a variety of thyroid lesions. The topo II labeling index is defined as the number of topo II staining positive nuclei divided by the total number of tumor cells counted multiplied by 100. An average of 1,000 cells were counted in each case. The average labeling indexes for anaplastic carcinoma (7.8), tall cell variant of papillary carcinoma (4.8), follicular carcinoma (2.6), Hürthle cell carcinoma (3.4), and medullary carcinoma (2.4) were much higher than for papillary carcinoma (0.76), follicular adenoma (0.65), Hürthle cell adenoma (0.32), and normal thyroid (0.1). This study suggests that immunohistochemical analysis of topo II correlates with thyroid tumor histology; it is more frequently expressed in tumors that are associated with aggressive clinical behavior. It may help to define a role for anti-topoisomerase drugs in treatment of aggressive thyroid neoplasms.
Insights
Topoisomerase II (topo II) expression is higher in aggressive thyroid tumors. Immunohistochemical analysis of topo II may guide treatment strategies for advanced thyroid cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Topoisomerase II (topo II) is crucial for DNA replication and chromosome segregation.
- Topo II is a validated target for antichemotherapeutic agents like etoposide.
- Differential expression of topo II isoforms in thyroid lesions is not well understood.
Purpose of the Study:
- To investigate the differential expression of topo IIalpha in various thyroid lesions using immunohistochemistry.
- To correlate topo II expression levels with thyroid tumor histology and clinical behavior.
Main Methods:
- Utilized a monoclonal antibody (Clone JH2.7) specific for topo IIalpha.
- Performed immunohistochemical analysis on a variety of thyroid lesions.
- Calculated the topo II labeling index (positive nuclei/total cells x 100), averaging 1,000 cells per case.
Main Results:
- Significantly higher average topo II labeling indexes were observed in aggressive thyroid carcinomas (anaplastic, tall cell variant papillary, follicular, Hürthle cell, medullary) compared to benign adenomas and normal thyroid tissue.
- Specifically, anaplastic carcinoma showed an average index of 7.8, while normal thyroid tissue had an average of 0.1.
- Papillary carcinoma (0.76), follicular adenoma (0.65), and Hürthle cell adenoma (0.32) exhibited low topo II expression.
Conclusions:
- Immunohistochemical analysis of topo II expression correlates with thyroid tumor histology.
- Elevated topo II expression is associated with more aggressive thyroid neoplasms.
- Topo II analysis may inform the use of anti-topoisomerase drugs for treating aggressive thyroid cancers.