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Published on: May 20, 2018
Comparative topoisomerase IIa and ki 67 protein expression in papillary thyroid carcinoma based on tissue microarrays
L Manaios1, E Tsiambas, M Alevizaki
1Department of Surgery, "Bioclinic", Athens, Greece.
Purpose:
Topoisomerase II alpha (Topo IIa gene location 17q21) is a nucleic enzyme involved in the DNA replication, transcription and chromosome topological formation. Topo IIa inhibition strategies include specific chemotherapeutic agents such as anthracyclines. Our aim was to investigate potential protein alterations of the enzyme comparing them to ki 67 proliferation marker expression in papillary thyroid carcinoma (PTC).
Materials And Methods:
Using tissue microarray (TMA) technology, 50 specimens consisting of histologically confirmed PTCs (n=20), multi-nodular goiters (n=20) and also normal thyroid epithelia (n=10) were cored and re-embedded in the final paraffin block. Immunohistochemical analysis was performed using monoclonal anti-Topo IIa and anti-ki 67 (MIB-1) antibodies. Digital image analysis assay was also applied for the evaluation of the protein expression results (Nuclear Labeling Index-NLI).
Results:
Topo IIa and ki 67 proteins were overexpressed in 4/20 (20%) and 14/20 (70%) cases, respectively. Concerning multi-nodular goiters, overexpression was observed in 2/20 and 4/20 specimens, respectively. Statistical association was assessed correlating ki 67 expression to pathology type, capsular invasion and also to vascular infiltration (p=0.001, p=0.008, and p=0.012, respectively). Topo IIa protein expression was strongly correlated only to capsular invasion (p=0.004). Overall expression of the examined markers demonstrated a medium concordance (kappa=0.27), but a strong association (p=0.001).
Conclusion:
Topo IIa and also ki 67 overexpression are correlated to an aggressive phenotype in PTC. Topo IIa overexpression maybe is a reliable marker for a rational application of targeted chemotherapeutic strategies in some subgroups of patients.
Insights
Topoisomerase II alpha (Topo IIa) and ki 67 overexpression indicate a more aggressive papillary thyroid carcinoma (PTC) phenotype. Topo IIa may guide targeted chemotherapy in specific PTC patient groups.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Topoisomerase II alpha (Topo IIa) is crucial for DNA replication and chromosome structure.
- Targeting Topo IIa with agents like anthracyclines is a chemotherapeutic strategy.
- Understanding Topo IIa alterations in papillary thyroid carcinoma (PTC) is important for treatment.
Purpose of the Study:
- To investigate Topoisomerase II alpha (Topo IIa) protein alterations in PTC.
- To compare Topo IIa expression with the ki 67 proliferation marker in PTC.
- To correlate these markers with clinicopathological features of PTC.
Main Methods:
- Tissue microarray (TMA) technology was used for 50 thyroid specimens (PTC, goiters, normal).
- Immunohistochemistry with anti-Topo IIa and anti-ki 67 antibodies was performed.
- Digital image analysis quantified protein expression (Nuclear Labeling Index).
Main Results:
- Topo IIa and ki 67 overexpression occurred in 20% and 70% of PTC cases, respectively.
- Ki 67 expression correlated significantly with pathology type, capsular, and vascular invasion (p<0.001).
- Topo IIa expression strongly correlated with capsular invasion (p=0.004).
Conclusions:
- Overexpression of Topo IIa and ki 67 is linked to an aggressive PTC phenotype.
- Topo IIa overexpression may serve as a marker for targeted chemotherapy selection in PTC.
- Further research can refine Topo IIa's role in personalized PTC treatment.
